Conference Coverage

BERLIN — Re-treatment with an antiepidermal growth factor receptor (EGFR) agent is effective in patients with chemorefractory metastatic colorectal cancer (mCRC) with RAS and BRAF wild-type tumors confirmed on circulating tumor DNA (ctDNA), although the sequencing of therapy does not seem to matter, suggest overall survival results from the crossover trial PARERE.

The findings nevertheless indicate that anti-EGFR rechallenge with panitumumab may prolong progression-free survival (PFS) over the multiple kinase inhibitor regorafenib. This suggests that “the most pragmatic choice” would be to give the anti-EGFR before regorafenib, said study presenter Marco Maria Germani, MD, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.

The caveat, however, is in patients who have an anti-EGFR interval since previously receiving the drugs of < 6 months. Those patients appeared to do better if they had regorafenib first and then anti-EGFR rechallenge.

Overall, Germani said that “since [trifluridine/tipiracil] plus bevacizumab is today the third-line standard of care” in this patient population, “anti-EGFR re-treatment might be considered after progression” on that combination.

Germani presented the research on October 18 at the European Society for Medical Oncology (ESMO) Annual Meeting 2025, which was simultaneously published in the Annals of Oncology.

Michel P. Ducreux, MD, PhD, head of the Digestive Cancer Committee at Gustave Roussy, Villejuif, France, and invited discussant for the results, said, despite the study being negative, it is “very important to continue to perform this kind of trial to evaluate the [ideal] sequence in the treatment of our patients.”

He continued that the secondary endpoints in the trial of PFS and objective response and disease control rates were “fairly in favor of the use of rechallenge before regorafenib, and in my opinion, this is really quite convincing.”

Ducreux, who was not involved in PARERE trail, also pointed to the sex difference seen in the study, which suggested that women responded much better to having anti-EGFR retreatment before regorafenib than did men.

Similar findings have been reported in a number of other trials, and previous work has suggested that there are sex differences in the pharmacokinetics of several anticancer drugs. However, while this is “very important,” he said that “we never consider it, because we are not able to really explain [it].”

Overall, he concluded that, on the basis of these results, he would agree with the notion that it is better to propose a rechallenge with anti-EGFR treatment as the fourth-line therapy in this patient population, before administering regorafenib.

Ducreux explained that, after a partial response, tumors acquire resistance to EGFR inhibitors through alterations and mutations that occur during treatment, via nongenetic mechanisms, and through treatment-induced selection for preexisting mutations.

Previous work has shown that mutations, such as in the RAS gene, are detectable early during EGFR inhibitor therapy, but that they then decay exponentially once the drugs are stopped, with the potential that tumors regain their sensitivity to them.

Germani said that this means that ctDNA-guided retreatment with anti-EGFR therapies is a “promising approach” in pretreated patients with RAS and BRAF wild-type mCRC, and that the sequencing of the drugs may be important. Indeed, the REVERCE trial showed that giving regorafenib followed by the anti-EGFR drug cetuzximab was associated with longer overall survival than the other way around in anti-EGFR medication-naive patients.

 

Methods and Results

For PARERE, the researchers enrolled patients aged at least 18 years with RAS and BRAF wild-type mCRC who were previously treated with a first-line anti-EGFR-containing regimen and had at least a partial response or stable disease for at least 6 months.

The patients were also required to have had at least one intervening anti-EGFR-free line of therapy, and to have previously received treatment with fluoropyrimidine, oxaliplatin, irinotecan, and anti-angiogenics. At least 4 months were required to have passed between the end of anti-EGFR administration and screening for the study.

In all, 428 patients were screened between December 2020 and December 2024, with 213 patients with RAS and BRAF wild-type mCRC, as detected on ctDNA, enrolled. They were randomized to panitumumab or regorafenib until first progression, followed by regorafenib, if they started on panitumumab, or panitumumab, if they started on regorafenib, until second progression.

The median age of the patients was 61 years among those who started on panitumumab and 64 years among those initially given regorafenib in the trial, and 63% and 57%, respectively, were male. The median number of prior lines of therapy was two in both groups, and 65% and 69%, respectively, had received pantitumumab as their first-line anti-EGFR.

Initial findings from the study presented at the 2025 ASCO Annual Meeting indicated that, after a median follow-up of 23.5 months, there was no significant difference in the median first PFS between the two treatment arms.

However, patients who started with panitumumab had a significant improvement in both the objective response and disease control rates (P < .001), as well as a signal for a potentially longer median second PFS, than those who started with regorafenib, particularly on the per-protocol analysis.

Presenting the overall survival results, Germani said that there was no significant difference between the groups on the intention-to-treat analysis, at a stratified hazard ratio of 1.13 (P = .440), or on the per-protocol analysis, at a hazard ratio of 1.07 (P = .730).

“We then ran a subgroup analysis,” he continued, “and we found out that an anti-EGFR-free interval before liquid biopsy shorter than 6 months was associated with less benefit from a panitumumab [first] sequence, which is biologically sound.”

It was also observed that women did significantly better when having panitumumab first, whereas men did not, for which “we do not have a clear biological explanation,” Germani added.

Confining the analysis to so-called “hyperselected” patients, who not only were RAS and BRAF wild type but also had no pathogenic mutations associated with anti-EGFR resistance, did not reveal any significant overall survival differences between the treatment groups.

However, Ducreux took issue with the way in which hyperselection, which is turning up more and more regularly in trials, is defined, as the choice of which mutations to include varies widely. He suggested that a consensus group be assembled to resolve this issue.

Looking more broadly, the researchers were able to show that, in this updated analysis, anti-EGFR re-treatment was superior to regorafenib regardless of the treatment sequence in terms of PFS, at 4.2 months vs 2.4 months (P = .103) when given first in the trial, and 3.9 months vs 2.7 months (P = .019) when given second in the trial, as well as in terms of objective response and disease control rates.

 

Adverse Events

In terms of safety, the results showed that, as expected, acneiform rash, fatigue, and hypomagnesemia were the most common adverse events associated with panitumumb, while those with regorafenib were fatigue, hand-foot skin reactions, and hypertension.

There were no notable differences in the number of patients receiving a post-study treatment nor in the post-study therapeutic choices, between the study arms.

The study was sponsored by GONO Foundation and partially supported by Amgen and Bayer. Germani declared having relationships with MSD and Amgen. Ducreux declared having relationships with Amgen, Bayer, BeiGene, Incyte, Jazz, Merck KGaA, Merck Serono, Merck Sharp & Dohme, Pierre Fabre, Roche, Servier, Keocyt, AbbVie, Abcely, Arcus, Bayer, BMS, Boehringer, GlaxoSmithKline, Sanofi, Scandion, and Zymeworks.

A version of this article first appeared on Medscape.com.

BERLIN — Re-treatment with an antiepidermal growth factor receptor (EGFR) agent is effective in patients with chemorefractory metastatic colorectal cancer (mCRC) with RAS and BRAF wild-type tumors confirmed on circulating tumor DNA (ctDNA), although the sequencing of therapy does not seem to matter, suggest overall survival results from the crossover trial PARERE.

The findings nevertheless indicate that anti-EGFR rechallenge with panitumumab may prolong progression-free survival (PFS) over the multiple kinase inhibitor regorafenib. This suggests that “the most pragmatic choice” would be to give the anti-EGFR before regorafenib, said study presenter Marco Maria Germani, MD, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.

The caveat, however, is in patients who have an anti-EGFR interval since previously receiving the drugs of < 6 months. Those patients appeared to do better if they had regorafenib first and then anti-EGFR rechallenge.

Overall, Germani said that “since [trifluridine/tipiracil] plus bevacizumab is today the third-line standard of care” in this patient population, “anti-EGFR re-treatment might be considered after progression” on that combination.

Germani presented the research on October 18 at the European Society for Medical Oncology (ESMO) Annual Meeting 2025, which was simultaneously published in the Annals of Oncology.

Michel P. Ducreux, MD, PhD, head of the Digestive Cancer Committee at Gustave Roussy, Villejuif, France, and invited discussant for the results, said, despite the study being negative, it is “very important to continue to perform this kind of trial to evaluate the [ideal] sequence in the treatment of our patients.”

He continued that the secondary endpoints in the trial of PFS and objective response and disease control rates were “fairly in favor of the use of rechallenge before regorafenib, and in my opinion, this is really quite convincing.”

Ducreux, who was not involved in PARERE trail, also pointed to the sex difference seen in the study, which suggested that women responded much better to having anti-EGFR retreatment before regorafenib than did men.

Similar findings have been reported in a number of other trials, and previous work has suggested that there are sex differences in the pharmacokinetics of several anticancer drugs. However, while this is “very important,” he said that “we never consider it, because we are not able to really explain [it].”

Overall, he concluded that, on the basis of these results, he would agree with the notion that it is better to propose a rechallenge with anti-EGFR treatment as the fourth-line therapy in this patient population, before administering regorafenib.

Ducreux explained that, after a partial response, tumors acquire resistance to EGFR inhibitors through alterations and mutations that occur during treatment, via nongenetic mechanisms, and through treatment-induced selection for preexisting mutations.

Previous work has shown that mutations, such as in the RAS gene, are detectable early during EGFR inhibitor therapy, but that they then decay exponentially once the drugs are stopped, with the potential that tumors regain their sensitivity to them.

Germani said that this means that ctDNA-guided retreatment with anti-EGFR therapies is a “promising approach” in pretreated patients with RAS and BRAF wild-type mCRC, and that the sequencing of the drugs may be important. Indeed, the REVERCE trial showed that giving regorafenib followed by the anti-EGFR drug cetuzximab was associated with longer overall survival than the other way around in anti-EGFR medication-naive patients.

 

Methods and Results

For PARERE, the researchers enrolled patients aged at least 18 years with RAS and BRAF wild-type mCRC who were previously treated with a first-line anti-EGFR-containing regimen and had at least a partial response or stable disease for at least 6 months.

The patients were also required to have had at least one intervening anti-EGFR-free line of therapy, and to have previously received treatment with fluoropyrimidine, oxaliplatin, irinotecan, and anti-angiogenics. At least 4 months were required to have passed between the end of anti-EGFR administration and screening for the study.

In all, 428 patients were screened between December 2020 and December 2024, with 213 patients with RAS and BRAF wild-type mCRC, as detected on ctDNA, enrolled. They were randomized to panitumumab or regorafenib until first progression, followed by regorafenib, if they started on panitumumab, or panitumumab, if they started on regorafenib, until second progression.

The median age of the patients was 61 years among those who started on panitumumab and 64 years among those initially given regorafenib in the trial, and 63% and 57%, respectively, were male. The median number of prior lines of therapy was two in both groups, and 65% and 69%, respectively, had received pantitumumab as their first-line anti-EGFR.

Initial findings from the study presented at the 2025 ASCO Annual Meeting indicated that, after a median follow-up of 23.5 months, there was no significant difference in the median first PFS between the two treatment arms.

However, patients who started with panitumumab had a significant improvement in both the objective response and disease control rates (P < .001), as well as a signal for a potentially longer median second PFS, than those who started with regorafenib, particularly on the per-protocol analysis.

Presenting the overall survival results, Germani said that there was no significant difference between the groups on the intention-to-treat analysis, at a stratified hazard ratio of 1.13 (P = .440), or on the per-protocol analysis, at a hazard ratio of 1.07 (P = .730).

“We then ran a subgroup analysis,” he continued, “and we found out that an anti-EGFR-free interval before liquid biopsy shorter than 6 months was associated with less benefit from a panitumumab [first] sequence, which is biologically sound.”

It was also observed that women did significantly better when having panitumumab first, whereas men did not, for which “we do not have a clear biological explanation,” Germani added.

Confining the analysis to so-called “hyperselected” patients, who not only were RAS and BRAF wild type but also had no pathogenic mutations associated with anti-EGFR resistance, did not reveal any significant overall survival differences between the treatment groups.

However, Ducreux took issue with the way in which hyperselection, which is turning up more and more regularly in trials, is defined, as the choice of which mutations to include varies widely. He suggested that a consensus group be assembled to resolve this issue.

Looking more broadly, the researchers were able to show that, in this updated analysis, anti-EGFR re-treatment was superior to regorafenib regardless of the treatment sequence in terms of PFS, at 4.2 months vs 2.4 months (P = .103) when given first in the trial, and 3.9 months vs 2.7 months (P = .019) when given second in the trial, as well as in terms of objective response and disease control rates.

 

Adverse Events

In terms of safety, the results showed that, as expected, acneiform rash, fatigue, and hypomagnesemia were the most common adverse events associated with panitumumb, while those with regorafenib were fatigue, hand-foot skin reactions, and hypertension.

There were no notable differences in the number of patients receiving a post-study treatment nor in the post-study therapeutic choices, between the study arms.

The study was sponsored by GONO Foundation and partially supported by Amgen and Bayer. Germani declared having relationships with MSD and Amgen. Ducreux declared having relationships with Amgen, Bayer, BeiGene, Incyte, Jazz, Merck KGaA, Merck Serono, Merck Sharp & Dohme, Pierre Fabre, Roche, Servier, Keocyt, AbbVie, Abcely, Arcus, Bayer, BMS, Boehringer, GlaxoSmithKline, Sanofi, Scandion, and Zymeworks.

A version of this article first appeared on Medscape.com.

BERLIN — Re-treatment with an antiepidermal growth factor receptor (EGFR) agent is effective in patients with chemorefractory metastatic colorectal cancer (mCRC) with RAS and BRAF wild-type tumors confirmed on circulating tumor DNA (ctDNA), although the sequencing of therapy does not seem to matter, suggest overall survival results from the crossover trial PARERE.

The findings nevertheless indicate that anti-EGFR rechallenge with panitumumab may prolong progression-free survival (PFS) over the multiple kinase inhibitor regorafenib. This suggests that “the most pragmatic choice” would be to give the anti-EGFR before regorafenib, said study presenter Marco Maria Germani, MD, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.

The caveat, however, is in patients who have an anti-EGFR interval since previously receiving the drugs of < 6 months. Those patients appeared to do better if they had regorafenib first and then anti-EGFR rechallenge.

Overall, Germani said that “since [trifluridine/tipiracil] plus bevacizumab is today the third-line standard of care” in this patient population, “anti-EGFR re-treatment might be considered after progression” on that combination.

Germani presented the research on October 18 at the European Society for Medical Oncology (ESMO) Annual Meeting 2025, which was simultaneously published in the Annals of Oncology.

Michel P. Ducreux, MD, PhD, head of the Digestive Cancer Committee at Gustave Roussy, Villejuif, France, and invited discussant for the results, said, despite the study being negative, it is “very important to continue to perform this kind of trial to evaluate the [ideal] sequence in the treatment of our patients.”

He continued that the secondary endpoints in the trial of PFS and objective response and disease control rates were “fairly in favor of the use of rechallenge before regorafenib, and in my opinion, this is really quite convincing.”

Ducreux, who was not involved in PARERE trail, also pointed to the sex difference seen in the study, which suggested that women responded much better to having anti-EGFR retreatment before regorafenib than did men.

Similar findings have been reported in a number of other trials, and previous work has suggested that there are sex differences in the pharmacokinetics of several anticancer drugs. However, while this is “very important,” he said that “we never consider it, because we are not able to really explain [it].”

Overall, he concluded that, on the basis of these results, he would agree with the notion that it is better to propose a rechallenge with anti-EGFR treatment as the fourth-line therapy in this patient population, before administering regorafenib.

Ducreux explained that, after a partial response, tumors acquire resistance to EGFR inhibitors through alterations and mutations that occur during treatment, via nongenetic mechanisms, and through treatment-induced selection for preexisting mutations.

Previous work has shown that mutations, such as in the RAS gene, are detectable early during EGFR inhibitor therapy, but that they then decay exponentially once the drugs are stopped, with the potential that tumors regain their sensitivity to them.

Germani said that this means that ctDNA-guided retreatment with anti-EGFR therapies is a “promising approach” in pretreated patients with RAS and BRAF wild-type mCRC, and that the sequencing of the drugs may be important. Indeed, the REVERCE trial showed that giving regorafenib followed by the anti-EGFR drug cetuzximab was associated with longer overall survival than the other way around in anti-EGFR medication-naive patients.

 

Methods and Results

For PARERE, the researchers enrolled patients aged at least 18 years with RAS and BRAF wild-type mCRC who were previously treated with a first-line anti-EGFR-containing regimen and had at least a partial response or stable disease for at least 6 months.

The patients were also required to have had at least one intervening anti-EGFR-free line of therapy, and to have previously received treatment with fluoropyrimidine, oxaliplatin, irinotecan, and anti-angiogenics. At least 4 months were required to have passed between the end of anti-EGFR administration and screening for the study.

In all, 428 patients were screened between December 2020 and December 2024, with 213 patients with RAS and BRAF wild-type mCRC, as detected on ctDNA, enrolled. They were randomized to panitumumab or regorafenib until first progression, followed by regorafenib, if they started on panitumumab, or panitumumab, if they started on regorafenib, until second progression.

The median age of the patients was 61 years among those who started on panitumumab and 64 years among those initially given regorafenib in the trial, and 63% and 57%, respectively, were male. The median number of prior lines of therapy was two in both groups, and 65% and 69%, respectively, had received pantitumumab as their first-line anti-EGFR.

Initial findings from the study presented at the 2025 ASCO Annual Meeting indicated that, after a median follow-up of 23.5 months, there was no significant difference in the median first PFS between the two treatment arms.

However, patients who started with panitumumab had a significant improvement in both the objective response and disease control rates (P < .001), as well as a signal for a potentially longer median second PFS, than those who started with regorafenib, particularly on the per-protocol analysis.

Presenting the overall survival results, Germani said that there was no significant difference between the groups on the intention-to-treat analysis, at a stratified hazard ratio of 1.13 (P = .440), or on the per-protocol analysis, at a hazard ratio of 1.07 (P = .730).

“We then ran a subgroup analysis,” he continued, “and we found out that an anti-EGFR-free interval before liquid biopsy shorter than 6 months was associated with less benefit from a panitumumab [first] sequence, which is biologically sound.”

It was also observed that women did significantly better when having panitumumab first, whereas men did not, for which “we do not have a clear biological explanation,” Germani added.

Confining the analysis to so-called “hyperselected” patients, who not only were RAS and BRAF wild type but also had no pathogenic mutations associated with anti-EGFR resistance, did not reveal any significant overall survival differences between the treatment groups.

However, Ducreux took issue with the way in which hyperselection, which is turning up more and more regularly in trials, is defined, as the choice of which mutations to include varies widely. He suggested that a consensus group be assembled to resolve this issue.

Looking more broadly, the researchers were able to show that, in this updated analysis, anti-EGFR re-treatment was superior to regorafenib regardless of the treatment sequence in terms of PFS, at 4.2 months vs 2.4 months (P = .103) when given first in the trial, and 3.9 months vs 2.7 months (P = .019) when given second in the trial, as well as in terms of objective response and disease control rates.

 

Adverse Events

In terms of safety, the results showed that, as expected, acneiform rash, fatigue, and hypomagnesemia were the most common adverse events associated with panitumumb, while those with regorafenib were fatigue, hand-foot skin reactions, and hypertension.

There were no notable differences in the number of patients receiving a post-study treatment nor in the post-study therapeutic choices, between the study arms.

The study was sponsored by GONO Foundation and partially supported by Amgen and Bayer. Germani declared having relationships with MSD and Amgen. Ducreux declared having relationships with Amgen, Bayer, BeiGene, Incyte, Jazz, Merck KGaA, Merck Serono, Merck Sharp & Dohme, Pierre Fabre, Roche, Servier, Keocyt, AbbVie, Abcely, Arcus, Bayer, BMS, Boehringer, GlaxoSmithKline, Sanofi, Scandion, and Zymeworks.

A version of this article first appeared on Medscape.com.

BERLIN — Patients with previously untreated locally recurrent inoperable or metastatic triple negative breast cancer (TNBC) who are not candidates for immunotherapy may experience improved survival outcomes with TROP2-directed antibody-drug conjugates (ADCs), suggested two trials presented at European Society for Medical Oncology (ESMO) Annual Meeting 2025 on October 19.

ASCENT-03 compared sacituzumab govitecan with standard of care chemotherapy, finding that the drug was associated with a 38% improvement in progression-free survival (PFS) in this patient population that has, traditionally, a poor prognosis. Overall survival data remain immature.

TROPION-Breast02 studied datopotamab deruxtecan (Dato-DXd) against investigator’s choice of chemotherapy. The PFS improvement with the ADC was 43%, while patients also experienced a 21% improvement in overall survival. In both cases, the safety profile of the experimental drugs was deemed to be manageable.

Discussant Ana C. Garrido-Castro, MD, director, Triple-Negative Breast Cancer Research, Dana-Farber Cancer Institute, Boston, who was not involved in either study, said that both sacituzumab govitecan and Dato-DXd showed a PFS benefit. The choice between them, leaving aside overall survival until the data are mature, will be largely based on factors such as the safety profile and the patient preference, she continued.

Sacituzumab govitecan is associated with an increase in neutropenia, nausea, and diarrhea, she pointed out, while Dato-DXd has increased rates of ocular surface toxicity, oral mucositis/stomatitis, and requires monitoring for interstitial lung disease.

Dato-DXd has a higher objective response rate than chemotherapy, unlike sacituzumab govitecan, but, crucially, requires one infusion vs 2 for sacituzumab govitecan per 21-day cycle, and has a shorter total infusion time.

There are nevertheless a number of unanswered questions about the drugs, including how the ADCs affect quality of life, and how common patient adherence to the recommended prophylaxis is. Patients with early relapse of < 12 months remain an “urgent unmet need,” Garrido-Castro said, and the role of immunotherapy rechallenge remains to be explored.

ADCs are also being tested in the neo-adjuvant TNBC setting, and the potential impact of that on the use of the drugs in the metastatic setting is currently unclear. In addition, there are questions around access to therapy.

“Ultimately, it will be very important to have a better understanding of the biomarkers of response and resistance and toxicity to these agents, and whether we should be sequencing antibody drug conjugates,” Garrido-Castro said. “All of this will help shape the next wave of treatment strategies for this patient population.”

She concluded: “Today, marks a paradigm shift of metastatic TNBC, in my opinion. ASCENT-03 and TROPION-Breast02 support TROP2 ADC therapy as the new preferred first-line regimen for this patient population.”

 

Method and Results of ASCENT-03

ASCENT-03 study presenter Javier C. Cortés, MD, PhD, International Breast Cancer Center, Pangaea Oncology, Quiron Group, Barcelona, Spain, said there is currently an unmet clinical need in the approximately 60% of patients with previously untreated metastatic TNBC who are not candidates for immune checkpoint inhibitors.

Median PFS in previous first-line studies was < 6 months with chemotherapy — the current standard of care — and Cortés said that around half of the patients who receive that in the first-line do not receive second-line therapy because of clinical deterioration or death.

“The sobering truth is that across studies in the US and Europe, approximately 25% to 30% of patients diagnosed with metastatic TNBC are no longer alive at 6 months from their metastatic diagnosis,” said Garrido-Castro. “So if there is a new drug that is able to significantly improve PFS with an acceptable toxicity profile, this should be sufficient to change the current standard of care in the first-line setting.”

As sacituzumab govitecan is already approved for second-line metastatic TNBC and for pretreated hormone receptor positive/HER2- metastatic breast cancer, the ASCENT-03 researchers studied the drug in patients with previously untreated locally advanced inoperable, or metastatic TNBC.

The patients were deemed not to be candidates for PD-L1 inhibitors through having PD-L1-negative tumors, by having PD-L1-positive tumors that had previously been treated with PD-L1 inhibitors in the curative setting, or by having a comorbidity that precluded PD-L1 inhibitor use.

The patients were required to have finished any prior treatment in the curative setting at least 6 months previously. Previously treated, stable central nervous system metastases were allowed.

They were randomized to sacituzumab govitecan or chemotherapy, comprising paclitaxel or nab-paclitaxel, or gemcitabine plus carboplatin, until progression, as verified by blinded independent central review (BICR), or unacceptable toxicity. Patients who progressed on chemotherapy were offered crossover to second-line sacituzumab govitecan.

In all, 558 patients were randomized. The median age was 56 years in the sacituzumab govitecan group vs 54 years in the chemotherapy group. The majority (64% in both groups) of patients were White individuals. The most common metastatic site was the lung (59% vs 61%), and 58% of patients in both groups had previously received a taxane.

Cortés reported that sacituzumab govitecan was associated with a “statistically significant and clinically meaningful” improvement in PFS by BICR, at a median of 9.7 months vs 6.9 months, or a hazard ratio (HR) of 0.62 (P < .0001). This benefit was seen across prespecified subgroups.

The objective response rate was almost identical between the two treatment groups, at 48% with sacituzumab govitecan vs 46% with chemotherapy, although the median duration of response was longer with the ADC, at 12.2 months vs 7.2 months.

Cortés showed the latest results on overall survival. This showed no significant difference between the two treatments, although he underlined that the data are not yet mature.

He also reported that the rates of grade ≥ 3 treatment-emergent adverse events (TEAEs) were similar in the two groups, at 66% with sacituzumab govitecan vs 62% with chemotherapy. However, the rates of TEAEs leading to treatment discontinuation (4% vs 12%) or dose reduction (37% vs 45%) were lower with the ADC.

Cortés concluded that the results suggest that sacituzumab govitecan “is a good option for patients with triple negative breast cancer when they develop metastasis and are unable to receive immune checkpoint inhibitors.”

 

TROPION-Breast02 Methods and Results

Presenting TROPION-Breast02, Rebecca A. Dent, MD, MSc, National Cancer Center Singapore and Duke-NUS Medical School, Singapore, explained that the trial looked at a patient population similar to that of ASCENT-03, here focusing instead on Dato-DXd.

Patients were included if they had histologically or cytologically documented locally recurrent inoperable or metastatic TNBC, no prior chemotherapy or targeted systemic therapy in this setting, and in whom immunotherapy was not an option.

They were randomized to Dato-DXd or the investigator’s choice of chemotherapy, with treatment continued until investigator-assessed progressive disease on RECIST v1.1, unacceptable toxicity, or another criterion for discontinuation was met.

In total, 642 patients were enrolled. The median age was 56 years for those in the Dato-DXd group and 57 years for those in chemotherapy group, and less than half (41% in the Dato-DXd group and 48% in the chemotherapy group) were White individuals. The number of metastatic sites was less than three in 64% and 67% of patients, respectively.

Dent showed that Dato-DXd was associated with a statistically significant and clinically meaningful improvement in BICR-assessed PFS, at a median of 10.8 months vs 5.6 months with chemotherapy, at a HR of 0.57 (P < .0001). The findings were replicated across the prespecified subgroups.

There was a marked overall survival benefit with Dato-DXd, at a median of 23.7 months vs 18.7 months, at a HR of 0.79 (P = .0291). Dent reported that, at 18 months, 61.2% of patients in the Dato-DXd group were still alive vs 51.3% in the chemotherapy group. Again, the benefit was seen across subgroups.

The confirmed objective response rate with Dato-DXd was far higher than that with chemotherapy, at 62.5% vs 29.3%, or an odds ratio of 4.24. The duration of response was also longer, at 12.3 months vs 7.1 months.

Rates of grade ≥ 3 adverse events were comparable, at 33% with Dato-DXd vs 29% with chemotherapy, although there were more events associated with dose reduction (27% vs 18%) and dose interruption (24% vs 19%) with the ADC.

“These results support Dato-DXd as the first new first-line standard of care for patients with locally recurrent inoperable or metastatic TNBC for whom immunotherapy is not an option,” Dent said.

“What’s important is the patients enrolled into this trial are clearly representative of real world patients that we are treating in our clinics every day. These patients are often excluded from our current clinical trials,” she said.

ASCENT-03 was funded by Gilead Sciences.

TROPION-Breast02 was funded by AstraZeneca.Cortés declared relationships with Roche, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Lilly, Merck Sharpe & Dohme, Leuko, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, HiberCell, BioInvent, GEMoaB, Gilead, Menarini, Zymeworks, Reveal Genomics, Expres2ion Biotechnologies, Jazz Pharmaceuticals, AbbVie, Scorpion Therapeutics, Bridgebio, Biocon, Biontech, Circle Pharma, Delcath Systems, Hexagon Bio, Novartis, Eisai, Pfizer, Stemline Therapeutics, MAJ3 Capital, Leuko, Ariad Pharmaceuticals, Baxalta GmbH/Servier Affaires, Bayer healthcare, Guardant Health, and PIQUR Therapeutics.

Dent declared relationships with AstraZeneca, MSD, Pfizer, Eisai, Novartis, Daiichi Sankyo/AstraZeneca, Roche, and Gilead Sciences.

Garrido-Castro declared relationships with AstraZeneca, MSD, Pfizer, Eisai, Novartis, Daiichi Sankyo/AstraZeneca, Roche, Gilead Sciences, Pfizer, TD Cowen, and Roche/Genentech.

A version of this article first appeared on Medscape.com.

BERLIN — Patients with previously untreated locally recurrent inoperable or metastatic triple negative breast cancer (TNBC) who are not candidates for immunotherapy may experience improved survival outcomes with TROP2-directed antibody-drug conjugates (ADCs), suggested two trials presented at European Society for Medical Oncology (ESMO) Annual Meeting 2025 on October 19.

ASCENT-03 compared sacituzumab govitecan with standard of care chemotherapy, finding that the drug was associated with a 38% improvement in progression-free survival (PFS) in this patient population that has, traditionally, a poor prognosis. Overall survival data remain immature.

TROPION-Breast02 studied datopotamab deruxtecan (Dato-DXd) against investigator’s choice of chemotherapy. The PFS improvement with the ADC was 43%, while patients also experienced a 21% improvement in overall survival. In both cases, the safety profile of the experimental drugs was deemed to be manageable.

Discussant Ana C. Garrido-Castro, MD, director, Triple-Negative Breast Cancer Research, Dana-Farber Cancer Institute, Boston, who was not involved in either study, said that both sacituzumab govitecan and Dato-DXd showed a PFS benefit. The choice between them, leaving aside overall survival until the data are mature, will be largely based on factors such as the safety profile and the patient preference, she continued.

Sacituzumab govitecan is associated with an increase in neutropenia, nausea, and diarrhea, she pointed out, while Dato-DXd has increased rates of ocular surface toxicity, oral mucositis/stomatitis, and requires monitoring for interstitial lung disease.

Dato-DXd has a higher objective response rate than chemotherapy, unlike sacituzumab govitecan, but, crucially, requires one infusion vs 2 for sacituzumab govitecan per 21-day cycle, and has a shorter total infusion time.

There are nevertheless a number of unanswered questions about the drugs, including how the ADCs affect quality of life, and how common patient adherence to the recommended prophylaxis is. Patients with early relapse of < 12 months remain an “urgent unmet need,” Garrido-Castro said, and the role of immunotherapy rechallenge remains to be explored.

ADCs are also being tested in the neo-adjuvant TNBC setting, and the potential impact of that on the use of the drugs in the metastatic setting is currently unclear. In addition, there are questions around access to therapy.

“Ultimately, it will be very important to have a better understanding of the biomarkers of response and resistance and toxicity to these agents, and whether we should be sequencing antibody drug conjugates,” Garrido-Castro said. “All of this will help shape the next wave of treatment strategies for this patient population.”

She concluded: “Today, marks a paradigm shift of metastatic TNBC, in my opinion. ASCENT-03 and TROPION-Breast02 support TROP2 ADC therapy as the new preferred first-line regimen for this patient population.”

 

Method and Results of ASCENT-03

ASCENT-03 study presenter Javier C. Cortés, MD, PhD, International Breast Cancer Center, Pangaea Oncology, Quiron Group, Barcelona, Spain, said there is currently an unmet clinical need in the approximately 60% of patients with previously untreated metastatic TNBC who are not candidates for immune checkpoint inhibitors.

Median PFS in previous first-line studies was < 6 months with chemotherapy — the current standard of care — and Cortés said that around half of the patients who receive that in the first-line do not receive second-line therapy because of clinical deterioration or death.

“The sobering truth is that across studies in the US and Europe, approximately 25% to 30% of patients diagnosed with metastatic TNBC are no longer alive at 6 months from their metastatic diagnosis,” said Garrido-Castro. “So if there is a new drug that is able to significantly improve PFS with an acceptable toxicity profile, this should be sufficient to change the current standard of care in the first-line setting.”

As sacituzumab govitecan is already approved for second-line metastatic TNBC and for pretreated hormone receptor positive/HER2- metastatic breast cancer, the ASCENT-03 researchers studied the drug in patients with previously untreated locally advanced inoperable, or metastatic TNBC.

The patients were deemed not to be candidates for PD-L1 inhibitors through having PD-L1-negative tumors, by having PD-L1-positive tumors that had previously been treated with PD-L1 inhibitors in the curative setting, or by having a comorbidity that precluded PD-L1 inhibitor use.

The patients were required to have finished any prior treatment in the curative setting at least 6 months previously. Previously treated, stable central nervous system metastases were allowed.

They were randomized to sacituzumab govitecan or chemotherapy, comprising paclitaxel or nab-paclitaxel, or gemcitabine plus carboplatin, until progression, as verified by blinded independent central review (BICR), or unacceptable toxicity. Patients who progressed on chemotherapy were offered crossover to second-line sacituzumab govitecan.

In all, 558 patients were randomized. The median age was 56 years in the sacituzumab govitecan group vs 54 years in the chemotherapy group. The majority (64% in both groups) of patients were White individuals. The most common metastatic site was the lung (59% vs 61%), and 58% of patients in both groups had previously received a taxane.

Cortés reported that sacituzumab govitecan was associated with a “statistically significant and clinically meaningful” improvement in PFS by BICR, at a median of 9.7 months vs 6.9 months, or a hazard ratio (HR) of 0.62 (P < .0001). This benefit was seen across prespecified subgroups.

The objective response rate was almost identical between the two treatment groups, at 48% with sacituzumab govitecan vs 46% with chemotherapy, although the median duration of response was longer with the ADC, at 12.2 months vs 7.2 months.

Cortés showed the latest results on overall survival. This showed no significant difference between the two treatments, although he underlined that the data are not yet mature.

He also reported that the rates of grade ≥ 3 treatment-emergent adverse events (TEAEs) were similar in the two groups, at 66% with sacituzumab govitecan vs 62% with chemotherapy. However, the rates of TEAEs leading to treatment discontinuation (4% vs 12%) or dose reduction (37% vs 45%) were lower with the ADC.

Cortés concluded that the results suggest that sacituzumab govitecan “is a good option for patients with triple negative breast cancer when they develop metastasis and are unable to receive immune checkpoint inhibitors.”

 

TROPION-Breast02 Methods and Results

Presenting TROPION-Breast02, Rebecca A. Dent, MD, MSc, National Cancer Center Singapore and Duke-NUS Medical School, Singapore, explained that the trial looked at a patient population similar to that of ASCENT-03, here focusing instead on Dato-DXd.

Patients were included if they had histologically or cytologically documented locally recurrent inoperable or metastatic TNBC, no prior chemotherapy or targeted systemic therapy in this setting, and in whom immunotherapy was not an option.

They were randomized to Dato-DXd or the investigator’s choice of chemotherapy, with treatment continued until investigator-assessed progressive disease on RECIST v1.1, unacceptable toxicity, or another criterion for discontinuation was met.

In total, 642 patients were enrolled. The median age was 56 years for those in the Dato-DXd group and 57 years for those in chemotherapy group, and less than half (41% in the Dato-DXd group and 48% in the chemotherapy group) were White individuals. The number of metastatic sites was less than three in 64% and 67% of patients, respectively.

Dent showed that Dato-DXd was associated with a statistically significant and clinically meaningful improvement in BICR-assessed PFS, at a median of 10.8 months vs 5.6 months with chemotherapy, at a HR of 0.57 (P < .0001). The findings were replicated across the prespecified subgroups.

There was a marked overall survival benefit with Dato-DXd, at a median of 23.7 months vs 18.7 months, at a HR of 0.79 (P = .0291). Dent reported that, at 18 months, 61.2% of patients in the Dato-DXd group were still alive vs 51.3% in the chemotherapy group. Again, the benefit was seen across subgroups.

The confirmed objective response rate with Dato-DXd was far higher than that with chemotherapy, at 62.5% vs 29.3%, or an odds ratio of 4.24. The duration of response was also longer, at 12.3 months vs 7.1 months.

Rates of grade ≥ 3 adverse events were comparable, at 33% with Dato-DXd vs 29% with chemotherapy, although there were more events associated with dose reduction (27% vs 18%) and dose interruption (24% vs 19%) with the ADC.

“These results support Dato-DXd as the first new first-line standard of care for patients with locally recurrent inoperable or metastatic TNBC for whom immunotherapy is not an option,” Dent said.

“What’s important is the patients enrolled into this trial are clearly representative of real world patients that we are treating in our clinics every day. These patients are often excluded from our current clinical trials,” she said.

ASCENT-03 was funded by Gilead Sciences.

TROPION-Breast02 was funded by AstraZeneca.Cortés declared relationships with Roche, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Lilly, Merck Sharpe & Dohme, Leuko, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, HiberCell, BioInvent, GEMoaB, Gilead, Menarini, Zymeworks, Reveal Genomics, Expres2ion Biotechnologies, Jazz Pharmaceuticals, AbbVie, Scorpion Therapeutics, Bridgebio, Biocon, Biontech, Circle Pharma, Delcath Systems, Hexagon Bio, Novartis, Eisai, Pfizer, Stemline Therapeutics, MAJ3 Capital, Leuko, Ariad Pharmaceuticals, Baxalta GmbH/Servier Affaires, Bayer healthcare, Guardant Health, and PIQUR Therapeutics.

Dent declared relationships with AstraZeneca, MSD, Pfizer, Eisai, Novartis, Daiichi Sankyo/AstraZeneca, Roche, and Gilead Sciences.

Garrido-Castro declared relationships with AstraZeneca, MSD, Pfizer, Eisai, Novartis, Daiichi Sankyo/AstraZeneca, Roche, Gilead Sciences, Pfizer, TD Cowen, and Roche/Genentech.

A version of this article first appeared on Medscape.com.

BERLIN — Patients with previously untreated locally recurrent inoperable or metastatic triple negative breast cancer (TNBC) who are not candidates for immunotherapy may experience improved survival outcomes with TROP2-directed antibody-drug conjugates (ADCs), suggested two trials presented at European Society for Medical Oncology (ESMO) Annual Meeting 2025 on October 19.

ASCENT-03 compared sacituzumab govitecan with standard of care chemotherapy, finding that the drug was associated with a 38% improvement in progression-free survival (PFS) in this patient population that has, traditionally, a poor prognosis. Overall survival data remain immature.

TROPION-Breast02 studied datopotamab deruxtecan (Dato-DXd) against investigator’s choice of chemotherapy. The PFS improvement with the ADC was 43%, while patients also experienced a 21% improvement in overall survival. In both cases, the safety profile of the experimental drugs was deemed to be manageable.

Discussant Ana C. Garrido-Castro, MD, director, Triple-Negative Breast Cancer Research, Dana-Farber Cancer Institute, Boston, who was not involved in either study, said that both sacituzumab govitecan and Dato-DXd showed a PFS benefit. The choice between them, leaving aside overall survival until the data are mature, will be largely based on factors such as the safety profile and the patient preference, she continued.

Sacituzumab govitecan is associated with an increase in neutropenia, nausea, and diarrhea, she pointed out, while Dato-DXd has increased rates of ocular surface toxicity, oral mucositis/stomatitis, and requires monitoring for interstitial lung disease.

Dato-DXd has a higher objective response rate than chemotherapy, unlike sacituzumab govitecan, but, crucially, requires one infusion vs 2 for sacituzumab govitecan per 21-day cycle, and has a shorter total infusion time.

There are nevertheless a number of unanswered questions about the drugs, including how the ADCs affect quality of life, and how common patient adherence to the recommended prophylaxis is. Patients with early relapse of < 12 months remain an “urgent unmet need,” Garrido-Castro said, and the role of immunotherapy rechallenge remains to be explored.

ADCs are also being tested in the neo-adjuvant TNBC setting, and the potential impact of that on the use of the drugs in the metastatic setting is currently unclear. In addition, there are questions around access to therapy.

“Ultimately, it will be very important to have a better understanding of the biomarkers of response and resistance and toxicity to these agents, and whether we should be sequencing antibody drug conjugates,” Garrido-Castro said. “All of this will help shape the next wave of treatment strategies for this patient population.”

She concluded: “Today, marks a paradigm shift of metastatic TNBC, in my opinion. ASCENT-03 and TROPION-Breast02 support TROP2 ADC therapy as the new preferred first-line regimen for this patient population.”

 

Method and Results of ASCENT-03

ASCENT-03 study presenter Javier C. Cortés, MD, PhD, International Breast Cancer Center, Pangaea Oncology, Quiron Group, Barcelona, Spain, said there is currently an unmet clinical need in the approximately 60% of patients with previously untreated metastatic TNBC who are not candidates for immune checkpoint inhibitors.

Median PFS in previous first-line studies was < 6 months with chemotherapy — the current standard of care — and Cortés said that around half of the patients who receive that in the first-line do not receive second-line therapy because of clinical deterioration or death.

“The sobering truth is that across studies in the US and Europe, approximately 25% to 30% of patients diagnosed with metastatic TNBC are no longer alive at 6 months from their metastatic diagnosis,” said Garrido-Castro. “So if there is a new drug that is able to significantly improve PFS with an acceptable toxicity profile, this should be sufficient to change the current standard of care in the first-line setting.”

As sacituzumab govitecan is already approved for second-line metastatic TNBC and for pretreated hormone receptor positive/HER2- metastatic breast cancer, the ASCENT-03 researchers studied the drug in patients with previously untreated locally advanced inoperable, or metastatic TNBC.

The patients were deemed not to be candidates for PD-L1 inhibitors through having PD-L1-negative tumors, by having PD-L1-positive tumors that had previously been treated with PD-L1 inhibitors in the curative setting, or by having a comorbidity that precluded PD-L1 inhibitor use.

The patients were required to have finished any prior treatment in the curative setting at least 6 months previously. Previously treated, stable central nervous system metastases were allowed.

They were randomized to sacituzumab govitecan or chemotherapy, comprising paclitaxel or nab-paclitaxel, or gemcitabine plus carboplatin, until progression, as verified by blinded independent central review (BICR), or unacceptable toxicity. Patients who progressed on chemotherapy were offered crossover to second-line sacituzumab govitecan.

In all, 558 patients were randomized. The median age was 56 years in the sacituzumab govitecan group vs 54 years in the chemotherapy group. The majority (64% in both groups) of patients were White individuals. The most common metastatic site was the lung (59% vs 61%), and 58% of patients in both groups had previously received a taxane.

Cortés reported that sacituzumab govitecan was associated with a “statistically significant and clinically meaningful” improvement in PFS by BICR, at a median of 9.7 months vs 6.9 months, or a hazard ratio (HR) of 0.62 (P < .0001). This benefit was seen across prespecified subgroups.

The objective response rate was almost identical between the two treatment groups, at 48% with sacituzumab govitecan vs 46% with chemotherapy, although the median duration of response was longer with the ADC, at 12.2 months vs 7.2 months.

Cortés showed the latest results on overall survival. This showed no significant difference between the two treatments, although he underlined that the data are not yet mature.

He also reported that the rates of grade ≥ 3 treatment-emergent adverse events (TEAEs) were similar in the two groups, at 66% with sacituzumab govitecan vs 62% with chemotherapy. However, the rates of TEAEs leading to treatment discontinuation (4% vs 12%) or dose reduction (37% vs 45%) were lower with the ADC.

Cortés concluded that the results suggest that sacituzumab govitecan “is a good option for patients with triple negative breast cancer when they develop metastasis and are unable to receive immune checkpoint inhibitors.”

 

TROPION-Breast02 Methods and Results

Presenting TROPION-Breast02, Rebecca A. Dent, MD, MSc, National Cancer Center Singapore and Duke-NUS Medical School, Singapore, explained that the trial looked at a patient population similar to that of ASCENT-03, here focusing instead on Dato-DXd.

Patients were included if they had histologically or cytologically documented locally recurrent inoperable or metastatic TNBC, no prior chemotherapy or targeted systemic therapy in this setting, and in whom immunotherapy was not an option.

They were randomized to Dato-DXd or the investigator’s choice of chemotherapy, with treatment continued until investigator-assessed progressive disease on RECIST v1.1, unacceptable toxicity, or another criterion for discontinuation was met.

In total, 642 patients were enrolled. The median age was 56 years for those in the Dato-DXd group and 57 years for those in chemotherapy group, and less than half (41% in the Dato-DXd group and 48% in the chemotherapy group) were White individuals. The number of metastatic sites was less than three in 64% and 67% of patients, respectively.

Dent showed that Dato-DXd was associated with a statistically significant and clinically meaningful improvement in BICR-assessed PFS, at a median of 10.8 months vs 5.6 months with chemotherapy, at a HR of 0.57 (P < .0001). The findings were replicated across the prespecified subgroups.

There was a marked overall survival benefit with Dato-DXd, at a median of 23.7 months vs 18.7 months, at a HR of 0.79 (P = .0291). Dent reported that, at 18 months, 61.2% of patients in the Dato-DXd group were still alive vs 51.3% in the chemotherapy group. Again, the benefit was seen across subgroups.

The confirmed objective response rate with Dato-DXd was far higher than that with chemotherapy, at 62.5% vs 29.3%, or an odds ratio of 4.24. The duration of response was also longer, at 12.3 months vs 7.1 months.

Rates of grade ≥ 3 adverse events were comparable, at 33% with Dato-DXd vs 29% with chemotherapy, although there were more events associated with dose reduction (27% vs 18%) and dose interruption (24% vs 19%) with the ADC.

“These results support Dato-DXd as the first new first-line standard of care for patients with locally recurrent inoperable or metastatic TNBC for whom immunotherapy is not an option,” Dent said.

“What’s important is the patients enrolled into this trial are clearly representative of real world patients that we are treating in our clinics every day. These patients are often excluded from our current clinical trials,” she said.

ASCENT-03 was funded by Gilead Sciences.

TROPION-Breast02 was funded by AstraZeneca.Cortés declared relationships with Roche, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Lilly, Merck Sharpe & Dohme, Leuko, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, HiberCell, BioInvent, GEMoaB, Gilead, Menarini, Zymeworks, Reveal Genomics, Expres2ion Biotechnologies, Jazz Pharmaceuticals, AbbVie, Scorpion Therapeutics, Bridgebio, Biocon, Biontech, Circle Pharma, Delcath Systems, Hexagon Bio, Novartis, Eisai, Pfizer, Stemline Therapeutics, MAJ3 Capital, Leuko, Ariad Pharmaceuticals, Baxalta GmbH/Servier Affaires, Bayer healthcare, Guardant Health, and PIQUR Therapeutics.

Dent declared relationships with AstraZeneca, MSD, Pfizer, Eisai, Novartis, Daiichi Sankyo/AstraZeneca, Roche, and Gilead Sciences.

Garrido-Castro declared relationships with AstraZeneca, MSD, Pfizer, Eisai, Novartis, Daiichi Sankyo/AstraZeneca, Roche, Gilead Sciences, Pfizer, TD Cowen, and Roche/Genentech.

A version of this article first appeared on Medscape.com.

BERLIN — Adding durvalumab (Imfinzi) to the standard perioperative regimen for patients with early adenocarcinoma of the upper gastrointestinal tract improves overall survival, according to findings presented at the 2025 annual meeting of the European Society for Medical Oncology (ESMO).

Experts said the survival benefit further supports perioperative durvalumab plus FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) as the new standard of care for patients with localized gastric or gastroesophageal adenocarcinoma. Earlier results from the phase 3 MATTERHORN trial, reported at the American Society of Clinical Oncology meeting (ASCO) in June, showed that the addition of durvalumab improved event-free survival compared with FLOT alone. 

The findings presented at ESMO show that at 36 months, overall survival was 68.6% among patients who received durvalumab + FLOT vs 61.9% among those given FLOT plus a placebo. After a median of 43 months, the survival advantage in the durvalumab group was statistically significant (hazard ratio [HR], 0.78; 95% CI, 0.63-0.96; P = .021) and “more importantly, clinically meaningful,” said lead investigator Josep Tabernero, MD, PhD, of Vall d’Hebron University Hospital in Barcelona.

The results “strongly support the use of perioperative durvalumab plus chemotherapy with FLOT as a new global standard of care for patients with localized gastric and gastroesophageal adenocarcinoma,” Tabernero said. 

Speaking as discussant for the session, Sylvie Lorenzen, MD, PhD, Technische Universität München in Munich, Germany, was enthusiastic that the previously reported trends in MATTERHORN held strong.

“The shape of the curves presented at ASCO was already very positive,” she said. “And now, with a longer follow-up, more events, and a higher overall survival maturity, they reach statistical significance. It looks like the magnitude of the effect increases with longer follow-up, and this is important for our patients.” 

The trial randomly assigned 948 patients with resectable gastric or gastroesophageal adenocarcinoma to receive either durvalumab (1500 mg) or placebo every 4 weeks, plus FLOT for 2 cycles before surgery and then again after, followed by durvalumab or placebo every 4 weeks for 10 cycles. 

Patients were stratified according to lymph node status, as well as PD-L1 expression (≥ 1% or < 1%, according to the Tumor Area Positivity score.)

The improvement in overall survival with durvalumab was seen regardless of PD-L1 expression, Tabernero said, with the same hazard ratios (0.79) in both the positive and negative subgroups.

However, there was no clear overall survival benefit in certain other subgroups, including women (n = 266; HR, 0.91), those with node-negative disease (n = 277; HR, 1.01), and those with diffuse histology (n = 249; HR, 0.98).

Lorenzen said that clinicians should “pay attention” to those patient subgroups, as they seem to benefit less from the addition of durvalumab. However, she cautioned that the findings were based on small patient numbers and the confidence intervals were wide.

Tabernero also reported additional data on event-free survival (EFS). Overall, the durvalumab/FLOT combination improved EFS among patients with any degree of pathological response and irrespective of lymph node status at surgery.

Regarding nodal staging, which was done in 800 patients, the percentage who achieved negative nodal status was higher in the durvalumab group (58.2%) vs the placebo group (44.8%). However, the improvement in EFS with durvalumab was comparable for node-negative (HR, 0.74) and node-positive (HR, 0.77) patients.

Lorenzen said that overall, the results provide a solid answer to the question, “Is it time to change practice?”

“I think MATTERHORN gives us the largest dataset and answers this question satisfactorily,” she said. Given that overall survival improved regardless of PD-L1 expression, she added, the combination of durvalumab and FLOT should be offered to “all our patient subgroups.”

The study was funded by AstraZeneca. Tabernero made numerous disclosures, including relationships with AstraZeneca, Boehringer Ingelheim, Chugai, and Daichii Sankyo. Lorenzen disclosed financial interests in or serving as an invited speaker for Servier, Lilly, MSD, and BMS.

A version of this article appeared on Medscape.com . 

BERLIN — Adding durvalumab (Imfinzi) to the standard perioperative regimen for patients with early adenocarcinoma of the upper gastrointestinal tract improves overall survival, according to findings presented at the 2025 annual meeting of the European Society for Medical Oncology (ESMO).

Experts said the survival benefit further supports perioperative durvalumab plus FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) as the new standard of care for patients with localized gastric or gastroesophageal adenocarcinoma. Earlier results from the phase 3 MATTERHORN trial, reported at the American Society of Clinical Oncology meeting (ASCO) in June, showed that the addition of durvalumab improved event-free survival compared with FLOT alone. 

The findings presented at ESMO show that at 36 months, overall survival was 68.6% among patients who received durvalumab + FLOT vs 61.9% among those given FLOT plus a placebo. After a median of 43 months, the survival advantage in the durvalumab group was statistically significant (hazard ratio [HR], 0.78; 95% CI, 0.63-0.96; P = .021) and “more importantly, clinically meaningful,” said lead investigator Josep Tabernero, MD, PhD, of Vall d’Hebron University Hospital in Barcelona.

The results “strongly support the use of perioperative durvalumab plus chemotherapy with FLOT as a new global standard of care for patients with localized gastric and gastroesophageal adenocarcinoma,” Tabernero said. 

Speaking as discussant for the session, Sylvie Lorenzen, MD, PhD, Technische Universität München in Munich, Germany, was enthusiastic that the previously reported trends in MATTERHORN held strong.

“The shape of the curves presented at ASCO was already very positive,” she said. “And now, with a longer follow-up, more events, and a higher overall survival maturity, they reach statistical significance. It looks like the magnitude of the effect increases with longer follow-up, and this is important for our patients.” 

The trial randomly assigned 948 patients with resectable gastric or gastroesophageal adenocarcinoma to receive either durvalumab (1500 mg) or placebo every 4 weeks, plus FLOT for 2 cycles before surgery and then again after, followed by durvalumab or placebo every 4 weeks for 10 cycles. 

Patients were stratified according to lymph node status, as well as PD-L1 expression (≥ 1% or < 1%, according to the Tumor Area Positivity score.)

The improvement in overall survival with durvalumab was seen regardless of PD-L1 expression, Tabernero said, with the same hazard ratios (0.79) in both the positive and negative subgroups.

However, there was no clear overall survival benefit in certain other subgroups, including women (n = 266; HR, 0.91), those with node-negative disease (n = 277; HR, 1.01), and those with diffuse histology (n = 249; HR, 0.98).

Lorenzen said that clinicians should “pay attention” to those patient subgroups, as they seem to benefit less from the addition of durvalumab. However, she cautioned that the findings were based on small patient numbers and the confidence intervals were wide.

Tabernero also reported additional data on event-free survival (EFS). Overall, the durvalumab/FLOT combination improved EFS among patients with any degree of pathological response and irrespective of lymph node status at surgery.

Regarding nodal staging, which was done in 800 patients, the percentage who achieved negative nodal status was higher in the durvalumab group (58.2%) vs the placebo group (44.8%). However, the improvement in EFS with durvalumab was comparable for node-negative (HR, 0.74) and node-positive (HR, 0.77) patients.

Lorenzen said that overall, the results provide a solid answer to the question, “Is it time to change practice?”

“I think MATTERHORN gives us the largest dataset and answers this question satisfactorily,” she said. Given that overall survival improved regardless of PD-L1 expression, she added, the combination of durvalumab and FLOT should be offered to “all our patient subgroups.”

The study was funded by AstraZeneca. Tabernero made numerous disclosures, including relationships with AstraZeneca, Boehringer Ingelheim, Chugai, and Daichii Sankyo. Lorenzen disclosed financial interests in or serving as an invited speaker for Servier, Lilly, MSD, and BMS.

A version of this article appeared on Medscape.com . 

BERLIN — Adding durvalumab (Imfinzi) to the standard perioperative regimen for patients with early adenocarcinoma of the upper gastrointestinal tract improves overall survival, according to findings presented at the 2025 annual meeting of the European Society for Medical Oncology (ESMO).

Experts said the survival benefit further supports perioperative durvalumab plus FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) as the new standard of care for patients with localized gastric or gastroesophageal adenocarcinoma. Earlier results from the phase 3 MATTERHORN trial, reported at the American Society of Clinical Oncology meeting (ASCO) in June, showed that the addition of durvalumab improved event-free survival compared with FLOT alone. 

The findings presented at ESMO show that at 36 months, overall survival was 68.6% among patients who received durvalumab + FLOT vs 61.9% among those given FLOT plus a placebo. After a median of 43 months, the survival advantage in the durvalumab group was statistically significant (hazard ratio [HR], 0.78; 95% CI, 0.63-0.96; P = .021) and “more importantly, clinically meaningful,” said lead investigator Josep Tabernero, MD, PhD, of Vall d’Hebron University Hospital in Barcelona.

The results “strongly support the use of perioperative durvalumab plus chemotherapy with FLOT as a new global standard of care for patients with localized gastric and gastroesophageal adenocarcinoma,” Tabernero said. 

Speaking as discussant for the session, Sylvie Lorenzen, MD, PhD, Technische Universität München in Munich, Germany, was enthusiastic that the previously reported trends in MATTERHORN held strong.

“The shape of the curves presented at ASCO was already very positive,” she said. “And now, with a longer follow-up, more events, and a higher overall survival maturity, they reach statistical significance. It looks like the magnitude of the effect increases with longer follow-up, and this is important for our patients.” 

The trial randomly assigned 948 patients with resectable gastric or gastroesophageal adenocarcinoma to receive either durvalumab (1500 mg) or placebo every 4 weeks, plus FLOT for 2 cycles before surgery and then again after, followed by durvalumab or placebo every 4 weeks for 10 cycles. 

Patients were stratified according to lymph node status, as well as PD-L1 expression (≥ 1% or < 1%, according to the Tumor Area Positivity score.)

The improvement in overall survival with durvalumab was seen regardless of PD-L1 expression, Tabernero said, with the same hazard ratios (0.79) in both the positive and negative subgroups.

However, there was no clear overall survival benefit in certain other subgroups, including women (n = 266; HR, 0.91), those with node-negative disease (n = 277; HR, 1.01), and those with diffuse histology (n = 249; HR, 0.98).

Lorenzen said that clinicians should “pay attention” to those patient subgroups, as they seem to benefit less from the addition of durvalumab. However, she cautioned that the findings were based on small patient numbers and the confidence intervals were wide.

Tabernero also reported additional data on event-free survival (EFS). Overall, the durvalumab/FLOT combination improved EFS among patients with any degree of pathological response and irrespective of lymph node status at surgery.

Regarding nodal staging, which was done in 800 patients, the percentage who achieved negative nodal status was higher in the durvalumab group (58.2%) vs the placebo group (44.8%). However, the improvement in EFS with durvalumab was comparable for node-negative (HR, 0.74) and node-positive (HR, 0.77) patients.

Lorenzen said that overall, the results provide a solid answer to the question, “Is it time to change practice?”

“I think MATTERHORN gives us the largest dataset and answers this question satisfactorily,” she said. Given that overall survival improved regardless of PD-L1 expression, she added, the combination of durvalumab and FLOT should be offered to “all our patient subgroups.”

The study was funded by AstraZeneca. Tabernero made numerous disclosures, including relationships with AstraZeneca, Boehringer Ingelheim, Chugai, and Daichii Sankyo. Lorenzen disclosed financial interests in or serving as an invited speaker for Servier, Lilly, MSD, and BMS.

A version of this article appeared on Medscape.com . 

BERLIN — Diet drinks may not be “healthier” than sugary drinks when it comes to liver health.

A large UK Biobank study found that higher intakes of both sugar-sweetened beverages (SSBs) and low- and non-SSBs (LNSSBs) were significantly associated with a higher risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD).

In fact, low- or artificially sweetened beverages were actually linked to a higher risk for MASLD than sugar-laden drinks, even at modest intake levels such as a single can per day.

“These findings challenge the common perception that these drinks are harmless and highlight the need to reconsider their role in diet and liver health, especially as MASLD emerges as a global health concern,” lead author Lihe Liu, a graduate student in the Department of Gastroenterology at The First Affiliated Hospital of Soochow University in Suzhou, China, said in a news release.

She presented her research at the United European Gastroenterology (UEG) Week 2025 in Berlin, Germany.

 

Stick With Water

MASLD affects 38% of the global population and has become a leading cause of cirrhosis, liver cancer, and liver-related death. Lifestyle modification remains “a cornerstone” of MASLD management. Current guidelines advise against SSBs, but the evidence regarding LNSSBs remains “limited,” Liu explained in her presentation.

To investigate, the researchers analyzed data of 123,788 UK Biobank participants without liver disease at baseline who were followed for an average of 10.3 years. Beverage consumption was assessed through repeated 24-hour dietary questionnaires using the question: “How many glasses, cans, or cartons containing 250 mL (roughly 250 g) of SSBs or LNSSBs did you drink yesterday?”

Intake was averaged across at least two recalls, and participants were grouped into three intake categories: none, more than 0 to one serving per day, or more than one serving per day.

The primary outcome was incident MASLD, and secondary outcomes included liver-related mortality and liver fat content measured using MRI-derived proton density fat fraction.

In the fully adjusted multivariable Cox model, compared with no consumption, consuming more than one serving of LNSSBs daily was associated with a 60% higher risk for MASLD (hazard ratio [HR], 1.599). The level of consumption of SSBs was associated with a 50% higher risk (HR, 1.469).

Consuming more than one serving of LNSSBs daily was also associated with a higher risk for severe liver outcomes (HR, 1.555), while SSBs showed no significant association after adjustment.

Neither SSBs nor LNSSBs showed significant associations with all-cause mortality in fully adjusted models.

Substituting either beverage with water reduced the risk for MASLD by 12.8% for SSBs and 15.2% for LNSSBs, Liu reported.

Both beverage types were positively associated with higher liver fat content. Consumption of more than one serving of SSBs and LNSSBs daily was associated with about 5% and 7% higher liver fat levels, respectively, than nonconsumption.

“The higher sugar content in SSBs can cause rapid spikes in blood glucose and insulin, promote weight gain, and increase uric acid levels, all of which contribute to liver fat accumulation. LNSSBs, on the other hand, may affect liver health by altering the gut microbiome, disrupting the feeling of fullness, driving sweet cravings, and even stimulating insulin secretion,” Liu said.

“The safest approach is to limit both sugar-sweetened and artificially sweetened drinks. Water remains the best choice as it removes the metabolic burden and prevents fat accumulation in the liver, whilst hydrating the body,” she concluded.

 

More Study Needed

Reached for comment, Sujit V. Janardhan, MD, PhD, director of the steatotic liver disease program, Rush University Medical Center, Chicago, said the findings “certainly should cause one to take pause from the popular notion that diet or non-sugar-sweetened beverages are healthier than their sugar-sweetened alternatives.”

He cautioned, however, that it would be “important to confirm confounders are adequately addressed in this large population-based study.”

“We must better understand what other exposure and characteristics were present in patients who had increased intake of non-sugar-sweetened beverages,” Janardhan told GI & Hepatology News.

“For example, it’s possible people who drank more non-sugar-sweetened beverages had more cardiovascular or metabolic risk factors (which prompted them to switch to the ‘diet’ alternative) and that it is these comorbidities that drove an association with increased MASLD incidence and liver-related mortality,” Janardhan noted.

“If there is one finding that seems easy to take away from this study, it’s that people who drank more water in place of sweetened beverages had reduced risk of MASLD,” he told GI & Hepatology News.

Therefore, while awaiting results of mechanistic studies and careful confounder analysis, “plain old boring water is your best bet,” Janardhan said.

The study had no specific funding. Liu and Janardhan had no relevant disclosures.

 

A version of this article appeared on Medscape.com.

BERLIN — Diet drinks may not be “healthier” than sugary drinks when it comes to liver health.

A large UK Biobank study found that higher intakes of both sugar-sweetened beverages (SSBs) and low- and non-SSBs (LNSSBs) were significantly associated with a higher risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD).

In fact, low- or artificially sweetened beverages were actually linked to a higher risk for MASLD than sugar-laden drinks, even at modest intake levels such as a single can per day.

“These findings challenge the common perception that these drinks are harmless and highlight the need to reconsider their role in diet and liver health, especially as MASLD emerges as a global health concern,” lead author Lihe Liu, a graduate student in the Department of Gastroenterology at The First Affiliated Hospital of Soochow University in Suzhou, China, said in a news release.

She presented her research at the United European Gastroenterology (UEG) Week 2025 in Berlin, Germany.

 

Stick With Water

MASLD affects 38% of the global population and has become a leading cause of cirrhosis, liver cancer, and liver-related death. Lifestyle modification remains “a cornerstone” of MASLD management. Current guidelines advise against SSBs, but the evidence regarding LNSSBs remains “limited,” Liu explained in her presentation.

To investigate, the researchers analyzed data of 123,788 UK Biobank participants without liver disease at baseline who were followed for an average of 10.3 years. Beverage consumption was assessed through repeated 24-hour dietary questionnaires using the question: “How many glasses, cans, or cartons containing 250 mL (roughly 250 g) of SSBs or LNSSBs did you drink yesterday?”

Intake was averaged across at least two recalls, and participants were grouped into three intake categories: none, more than 0 to one serving per day, or more than one serving per day.

The primary outcome was incident MASLD, and secondary outcomes included liver-related mortality and liver fat content measured using MRI-derived proton density fat fraction.

In the fully adjusted multivariable Cox model, compared with no consumption, consuming more than one serving of LNSSBs daily was associated with a 60% higher risk for MASLD (hazard ratio [HR], 1.599). The level of consumption of SSBs was associated with a 50% higher risk (HR, 1.469).

Consuming more than one serving of LNSSBs daily was also associated with a higher risk for severe liver outcomes (HR, 1.555), while SSBs showed no significant association after adjustment.

Neither SSBs nor LNSSBs showed significant associations with all-cause mortality in fully adjusted models.

Substituting either beverage with water reduced the risk for MASLD by 12.8% for SSBs and 15.2% for LNSSBs, Liu reported.

Both beverage types were positively associated with higher liver fat content. Consumption of more than one serving of SSBs and LNSSBs daily was associated with about 5% and 7% higher liver fat levels, respectively, than nonconsumption.

“The higher sugar content in SSBs can cause rapid spikes in blood glucose and insulin, promote weight gain, and increase uric acid levels, all of which contribute to liver fat accumulation. LNSSBs, on the other hand, may affect liver health by altering the gut microbiome, disrupting the feeling of fullness, driving sweet cravings, and even stimulating insulin secretion,” Liu said.

“The safest approach is to limit both sugar-sweetened and artificially sweetened drinks. Water remains the best choice as it removes the metabolic burden and prevents fat accumulation in the liver, whilst hydrating the body,” she concluded.

 

More Study Needed

Reached for comment, Sujit V. Janardhan, MD, PhD, director of the steatotic liver disease program, Rush University Medical Center, Chicago, said the findings “certainly should cause one to take pause from the popular notion that diet or non-sugar-sweetened beverages are healthier than their sugar-sweetened alternatives.”

He cautioned, however, that it would be “important to confirm confounders are adequately addressed in this large population-based study.”

“We must better understand what other exposure and characteristics were present in patients who had increased intake of non-sugar-sweetened beverages,” Janardhan told GI & Hepatology News.

“For example, it’s possible people who drank more non-sugar-sweetened beverages had more cardiovascular or metabolic risk factors (which prompted them to switch to the ‘diet’ alternative) and that it is these comorbidities that drove an association with increased MASLD incidence and liver-related mortality,” Janardhan noted.

“If there is one finding that seems easy to take away from this study, it’s that people who drank more water in place of sweetened beverages had reduced risk of MASLD,” he told GI & Hepatology News.

Therefore, while awaiting results of mechanistic studies and careful confounder analysis, “plain old boring water is your best bet,” Janardhan said.

The study had no specific funding. Liu and Janardhan had no relevant disclosures.

 

A version of this article appeared on Medscape.com.

BERLIN — Diet drinks may not be “healthier” than sugary drinks when it comes to liver health.

A large UK Biobank study found that higher intakes of both sugar-sweetened beverages (SSBs) and low- and non-SSBs (LNSSBs) were significantly associated with a higher risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD).

In fact, low- or artificially sweetened beverages were actually linked to a higher risk for MASLD than sugar-laden drinks, even at modest intake levels such as a single can per day.

“These findings challenge the common perception that these drinks are harmless and highlight the need to reconsider their role in diet and liver health, especially as MASLD emerges as a global health concern,” lead author Lihe Liu, a graduate student in the Department of Gastroenterology at The First Affiliated Hospital of Soochow University in Suzhou, China, said in a news release.

She presented her research at the United European Gastroenterology (UEG) Week 2025 in Berlin, Germany.

 

Stick With Water

MASLD affects 38% of the global population and has become a leading cause of cirrhosis, liver cancer, and liver-related death. Lifestyle modification remains “a cornerstone” of MASLD management. Current guidelines advise against SSBs, but the evidence regarding LNSSBs remains “limited,” Liu explained in her presentation.

To investigate, the researchers analyzed data of 123,788 UK Biobank participants without liver disease at baseline who were followed for an average of 10.3 years. Beverage consumption was assessed through repeated 24-hour dietary questionnaires using the question: “How many glasses, cans, or cartons containing 250 mL (roughly 250 g) of SSBs or LNSSBs did you drink yesterday?”

Intake was averaged across at least two recalls, and participants were grouped into three intake categories: none, more than 0 to one serving per day, or more than one serving per day.

The primary outcome was incident MASLD, and secondary outcomes included liver-related mortality and liver fat content measured using MRI-derived proton density fat fraction.

In the fully adjusted multivariable Cox model, compared with no consumption, consuming more than one serving of LNSSBs daily was associated with a 60% higher risk for MASLD (hazard ratio [HR], 1.599). The level of consumption of SSBs was associated with a 50% higher risk (HR, 1.469).

Consuming more than one serving of LNSSBs daily was also associated with a higher risk for severe liver outcomes (HR, 1.555), while SSBs showed no significant association after adjustment.

Neither SSBs nor LNSSBs showed significant associations with all-cause mortality in fully adjusted models.

Substituting either beverage with water reduced the risk for MASLD by 12.8% for SSBs and 15.2% for LNSSBs, Liu reported.

Both beverage types were positively associated with higher liver fat content. Consumption of more than one serving of SSBs and LNSSBs daily was associated with about 5% and 7% higher liver fat levels, respectively, than nonconsumption.

“The higher sugar content in SSBs can cause rapid spikes in blood glucose and insulin, promote weight gain, and increase uric acid levels, all of which contribute to liver fat accumulation. LNSSBs, on the other hand, may affect liver health by altering the gut microbiome, disrupting the feeling of fullness, driving sweet cravings, and even stimulating insulin secretion,” Liu said.

“The safest approach is to limit both sugar-sweetened and artificially sweetened drinks. Water remains the best choice as it removes the metabolic burden and prevents fat accumulation in the liver, whilst hydrating the body,” she concluded.

 

More Study Needed

Reached for comment, Sujit V. Janardhan, MD, PhD, director of the steatotic liver disease program, Rush University Medical Center, Chicago, said the findings “certainly should cause one to take pause from the popular notion that diet or non-sugar-sweetened beverages are healthier than their sugar-sweetened alternatives.”

He cautioned, however, that it would be “important to confirm confounders are adequately addressed in this large population-based study.”

“We must better understand what other exposure and characteristics were present in patients who had increased intake of non-sugar-sweetened beverages,” Janardhan told GI & Hepatology News.

“For example, it’s possible people who drank more non-sugar-sweetened beverages had more cardiovascular or metabolic risk factors (which prompted them to switch to the ‘diet’ alternative) and that it is these comorbidities that drove an association with increased MASLD incidence and liver-related mortality,” Janardhan noted.

“If there is one finding that seems easy to take away from this study, it’s that people who drank more water in place of sweetened beverages had reduced risk of MASLD,” he told GI & Hepatology News.

Therefore, while awaiting results of mechanistic studies and careful confounder analysis, “plain old boring water is your best bet,” Janardhan said.

The study had no specific funding. Liu and Janardhan had no relevant disclosures.

 

A version of this article appeared on Medscape.com.

BERLIN — Women who use menopausal hormone therapy (MHT; ie, hormone replacement therapy ) have an up to 30% reduction in the risk of developing esophageal and gastric cancers compared to nonusers, according to a large population-based study across five Nordic countries. The association appeared strongest for combined estrogen-progestin and systemic formulations.

“This is one of the largest and most comprehensive studies to date supporting the hypothesis of an inverse association between MHT and risk of esophago-gastric cancer,” said Victoria Wocalewski, MD, from the Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, who presented the findings at United European Gastroenterology (UEG) Week 2025. 

There was a decreased risk for all investigated cancers in MHT users, but the strongest association was observed for esophageal adenocarcinoma (EAC), said Wocalewski. In addition, “there were discrete dose-dependent results for [EAC] and gastric adenocarcinoma (GAC) but not for esophageal squamous cell carcinoma (ESCC).”

 

Large Population-Based Study 

Previous research has suggested that hormonal changes could partly explain the male predominance in esophageal and gastric cancers, but evidence from large, well-controlled datasets has been limited. 

“Cancer rates in women increase significantly after age of 60, so it has been hypothesized that this pattern is linked to declined levels of estrogen that comes with menopause,” said Wocalewski, explaining the rationale for the study.

“Some studies looking at MHT use have indicated a possible protective effect, but with some contradictory results and type-specific variations,” Wocalewski noted. “Our study aimed to investigate these previous findings using a larger study sample.”

The population-based case-control study drew on prospectively collected data from the NordGETS database including national prescription, cancer, and population registries in Denmark, Finland, Iceland, Norway, and Sweden spanning 1994-2020. In total, 19,518 women with esophago-gastric cancer were compared with 195,094 controls randomly selected from the general population, and matched for age, calendar year, and country (in a 1:10 ratio). Women were 45 years or over with a diagnosis of EAC, ESCC, or GAC. 

In total there were 5000 cases of EAC, 4401 of ESCC, and 10,117 of GAC, with the median ages being 74, 72, and 75 years, respectively; most cases of EAC and ESCC were found in Denmark, and most cases of GAC were in Sweden. 

The investigators categorized participants by defined daily doses (DDDs) of MHT into three equal sized categories: low (< 158 DDDs), intermediate (158-848 DDDs), and high (> 848 DDDs). MHT was defined as systemic or local, and estrogen only or combined with progesterone. Odds ratios (ORs) were calculated for three major cancer outcomes of EAC, ESCC, and GAC, adjusted for known confounders such as age, obesity, smoking, alcohol consumption, reflux disease, Helicobacter pylori eradication, and concomitant use of statins or non-steroidal anti-inflammatory drugs (NSAIDs). However, Wocalewski noted that they did not adjust for socio-economic factors. 

 

Significant Reductions Across Esophago-Gastric Cancers

Compared with nonusers, women with any MHT exposure had a markedly reduced risk of EAC with adjusted ORs (aORs) of 0.74 (95% CI, 0.67-0.81) for low-use, 0.68 (95% CI, 0.61-0.75) for intermediate-use, and 0.68 (95% CI, 0.61-0.75) for high-use groups. Various adjustments were made for obesity, reflux, statins, and NSAIDs, as well as smoking, alcohol use, and H pylori eradication.

Similar inverse associations were seen for ESCC with aORs of 0.69 (95% CI, 0.62-0.77), 0.70 (95% CI, 0.62-0.77), and 0.71 (95% CI, 0.64-0.79) across the dose categories, and for GAC where risk decreased progressively from 0.90 (95% CI, 0.84-0.96) to 0.80 (95% CI, 0.74-0.86) across increasing MHT doses.

When stratified by hormone formulation, combined estrogen-progesterone therapy and systemic MHT conferred the strongest risk reduction. For example, systemic MHT use was associated with aORs of 0.67 (95% CI, 0.61-0.74) for EAC and 0.82 (95% CI, 0.76-0.88) for GAC, while local (vaginal) preparations showed slightly weaker associations at 0.72 (95% CI, 0.66-0.78) and 0.87 (95% CI, 0.83-0.92), respectively. 

In EAC, combined estrogen-progesterone therapy led to an OR of 0.68 (95% CI, 0.63-0.73) and 0.77 (95% CI, 0.69-0.87) for women on estrogen alone. Similar results were found for ESCC. For GAC, combination resulted in an aOR of 0.85 (95% CI, 0.80-0.89) and 0.88 (95% CI, 0.81-0.97) in estrogen only therapy respectively.

“Our results reinforce the concept that estrogenic signaling may influence tumor development in the upper GI tract,” said Wocalewski. “Understanding these mechanisms could help identify at-risk populations and inform prevention strategies,” she added, noting that, “hormonal effects on epithelial tight junctions and nitric oxide synthesis in the gastrointestinal tract” would have an influence on smooth muscle cells.

 

Link Between Hormones and GI Pathology

Commenting on the study for GI & Hepatology News, Jan Bornschein, MD, University of Oxford, UK, who was not involved in the research, said the results are “highly relevant.” 

“We’ve seen for a long time a link between hormones and GI pathology, however, it has been poorly investigated and the whole mechanisms are not understood, so it’s welcome that this group is moving forward and investigating this in a structured way,” he said.

Another delegate cautioned that MHT was associated with a risk for other non- gastrointestinal cancers. “I think it’s extremely important, because there are data on associations [of MHT] with breast cancer and also endometrial cancer. It’s good to see that it may help and reduce this cancer, but we have to be really careful about the others.”

Wocalewski reports no relevant conflicts of interest. Bornschein has no disclosures relevant to this study. The study was funded by Karolinska Institutet and supported by national cancer and prescription registry data from Denmark, Finland, Iceland, Norway, and Sweden.

 

A version of this article appeared on Medscape.com.

BERLIN — Women who use menopausal hormone therapy (MHT; ie, hormone replacement therapy ) have an up to 30% reduction in the risk of developing esophageal and gastric cancers compared to nonusers, according to a large population-based study across five Nordic countries. The association appeared strongest for combined estrogen-progestin and systemic formulations.

“This is one of the largest and most comprehensive studies to date supporting the hypothesis of an inverse association between MHT and risk of esophago-gastric cancer,” said Victoria Wocalewski, MD, from the Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, who presented the findings at United European Gastroenterology (UEG) Week 2025. 

There was a decreased risk for all investigated cancers in MHT users, but the strongest association was observed for esophageal adenocarcinoma (EAC), said Wocalewski. In addition, “there were discrete dose-dependent results for [EAC] and gastric adenocarcinoma (GAC) but not for esophageal squamous cell carcinoma (ESCC).”

 

Large Population-Based Study 

Previous research has suggested that hormonal changes could partly explain the male predominance in esophageal and gastric cancers, but evidence from large, well-controlled datasets has been limited. 

“Cancer rates in women increase significantly after age of 60, so it has been hypothesized that this pattern is linked to declined levels of estrogen that comes with menopause,” said Wocalewski, explaining the rationale for the study.

“Some studies looking at MHT use have indicated a possible protective effect, but with some contradictory results and type-specific variations,” Wocalewski noted. “Our study aimed to investigate these previous findings using a larger study sample.”

The population-based case-control study drew on prospectively collected data from the NordGETS database including national prescription, cancer, and population registries in Denmark, Finland, Iceland, Norway, and Sweden spanning 1994-2020. In total, 19,518 women with esophago-gastric cancer were compared with 195,094 controls randomly selected from the general population, and matched for age, calendar year, and country (in a 1:10 ratio). Women were 45 years or over with a diagnosis of EAC, ESCC, or GAC. 

In total there were 5000 cases of EAC, 4401 of ESCC, and 10,117 of GAC, with the median ages being 74, 72, and 75 years, respectively; most cases of EAC and ESCC were found in Denmark, and most cases of GAC were in Sweden. 

The investigators categorized participants by defined daily doses (DDDs) of MHT into three equal sized categories: low (< 158 DDDs), intermediate (158-848 DDDs), and high (> 848 DDDs). MHT was defined as systemic or local, and estrogen only or combined with progesterone. Odds ratios (ORs) were calculated for three major cancer outcomes of EAC, ESCC, and GAC, adjusted for known confounders such as age, obesity, smoking, alcohol consumption, reflux disease, Helicobacter pylori eradication, and concomitant use of statins or non-steroidal anti-inflammatory drugs (NSAIDs). However, Wocalewski noted that they did not adjust for socio-economic factors. 

 

Significant Reductions Across Esophago-Gastric Cancers

Compared with nonusers, women with any MHT exposure had a markedly reduced risk of EAC with adjusted ORs (aORs) of 0.74 (95% CI, 0.67-0.81) for low-use, 0.68 (95% CI, 0.61-0.75) for intermediate-use, and 0.68 (95% CI, 0.61-0.75) for high-use groups. Various adjustments were made for obesity, reflux, statins, and NSAIDs, as well as smoking, alcohol use, and H pylori eradication.

Similar inverse associations were seen for ESCC with aORs of 0.69 (95% CI, 0.62-0.77), 0.70 (95% CI, 0.62-0.77), and 0.71 (95% CI, 0.64-0.79) across the dose categories, and for GAC where risk decreased progressively from 0.90 (95% CI, 0.84-0.96) to 0.80 (95% CI, 0.74-0.86) across increasing MHT doses.

When stratified by hormone formulation, combined estrogen-progesterone therapy and systemic MHT conferred the strongest risk reduction. For example, systemic MHT use was associated with aORs of 0.67 (95% CI, 0.61-0.74) for EAC and 0.82 (95% CI, 0.76-0.88) for GAC, while local (vaginal) preparations showed slightly weaker associations at 0.72 (95% CI, 0.66-0.78) and 0.87 (95% CI, 0.83-0.92), respectively. 

In EAC, combined estrogen-progesterone therapy led to an OR of 0.68 (95% CI, 0.63-0.73) and 0.77 (95% CI, 0.69-0.87) for women on estrogen alone. Similar results were found for ESCC. For GAC, combination resulted in an aOR of 0.85 (95% CI, 0.80-0.89) and 0.88 (95% CI, 0.81-0.97) in estrogen only therapy respectively.

“Our results reinforce the concept that estrogenic signaling may influence tumor development in the upper GI tract,” said Wocalewski. “Understanding these mechanisms could help identify at-risk populations and inform prevention strategies,” she added, noting that, “hormonal effects on epithelial tight junctions and nitric oxide synthesis in the gastrointestinal tract” would have an influence on smooth muscle cells.

 

Link Between Hormones and GI Pathology

Commenting on the study for GI & Hepatology News, Jan Bornschein, MD, University of Oxford, UK, who was not involved in the research, said the results are “highly relevant.” 

“We’ve seen for a long time a link between hormones and GI pathology, however, it has been poorly investigated and the whole mechanisms are not understood, so it’s welcome that this group is moving forward and investigating this in a structured way,” he said.

Another delegate cautioned that MHT was associated with a risk for other non- gastrointestinal cancers. “I think it’s extremely important, because there are data on associations [of MHT] with breast cancer and also endometrial cancer. It’s good to see that it may help and reduce this cancer, but we have to be really careful about the others.”

Wocalewski reports no relevant conflicts of interest. Bornschein has no disclosures relevant to this study. The study was funded by Karolinska Institutet and supported by national cancer and prescription registry data from Denmark, Finland, Iceland, Norway, and Sweden.

 

A version of this article appeared on Medscape.com.

BERLIN — Women who use menopausal hormone therapy (MHT; ie, hormone replacement therapy ) have an up to 30% reduction in the risk of developing esophageal and gastric cancers compared to nonusers, according to a large population-based study across five Nordic countries. The association appeared strongest for combined estrogen-progestin and systemic formulations.

“This is one of the largest and most comprehensive studies to date supporting the hypothesis of an inverse association between MHT and risk of esophago-gastric cancer,” said Victoria Wocalewski, MD, from the Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, who presented the findings at United European Gastroenterology (UEG) Week 2025. 

There was a decreased risk for all investigated cancers in MHT users, but the strongest association was observed for esophageal adenocarcinoma (EAC), said Wocalewski. In addition, “there were discrete dose-dependent results for [EAC] and gastric adenocarcinoma (GAC) but not for esophageal squamous cell carcinoma (ESCC).”

 

Large Population-Based Study 

Previous research has suggested that hormonal changes could partly explain the male predominance in esophageal and gastric cancers, but evidence from large, well-controlled datasets has been limited. 

“Cancer rates in women increase significantly after age of 60, so it has been hypothesized that this pattern is linked to declined levels of estrogen that comes with menopause,” said Wocalewski, explaining the rationale for the study.

“Some studies looking at MHT use have indicated a possible protective effect, but with some contradictory results and type-specific variations,” Wocalewski noted. “Our study aimed to investigate these previous findings using a larger study sample.”

The population-based case-control study drew on prospectively collected data from the NordGETS database including national prescription, cancer, and population registries in Denmark, Finland, Iceland, Norway, and Sweden spanning 1994-2020. In total, 19,518 women with esophago-gastric cancer were compared with 195,094 controls randomly selected from the general population, and matched for age, calendar year, and country (in a 1:10 ratio). Women were 45 years or over with a diagnosis of EAC, ESCC, or GAC. 

In total there were 5000 cases of EAC, 4401 of ESCC, and 10,117 of GAC, with the median ages being 74, 72, and 75 years, respectively; most cases of EAC and ESCC were found in Denmark, and most cases of GAC were in Sweden. 

The investigators categorized participants by defined daily doses (DDDs) of MHT into three equal sized categories: low (< 158 DDDs), intermediate (158-848 DDDs), and high (> 848 DDDs). MHT was defined as systemic or local, and estrogen only or combined with progesterone. Odds ratios (ORs) were calculated for three major cancer outcomes of EAC, ESCC, and GAC, adjusted for known confounders such as age, obesity, smoking, alcohol consumption, reflux disease, Helicobacter pylori eradication, and concomitant use of statins or non-steroidal anti-inflammatory drugs (NSAIDs). However, Wocalewski noted that they did not adjust for socio-economic factors. 

 

Significant Reductions Across Esophago-Gastric Cancers

Compared with nonusers, women with any MHT exposure had a markedly reduced risk of EAC with adjusted ORs (aORs) of 0.74 (95% CI, 0.67-0.81) for low-use, 0.68 (95% CI, 0.61-0.75) for intermediate-use, and 0.68 (95% CI, 0.61-0.75) for high-use groups. Various adjustments were made for obesity, reflux, statins, and NSAIDs, as well as smoking, alcohol use, and H pylori eradication.

Similar inverse associations were seen for ESCC with aORs of 0.69 (95% CI, 0.62-0.77), 0.70 (95% CI, 0.62-0.77), and 0.71 (95% CI, 0.64-0.79) across the dose categories, and for GAC where risk decreased progressively from 0.90 (95% CI, 0.84-0.96) to 0.80 (95% CI, 0.74-0.86) across increasing MHT doses.

When stratified by hormone formulation, combined estrogen-progesterone therapy and systemic MHT conferred the strongest risk reduction. For example, systemic MHT use was associated with aORs of 0.67 (95% CI, 0.61-0.74) for EAC and 0.82 (95% CI, 0.76-0.88) for GAC, while local (vaginal) preparations showed slightly weaker associations at 0.72 (95% CI, 0.66-0.78) and 0.87 (95% CI, 0.83-0.92), respectively. 

In EAC, combined estrogen-progesterone therapy led to an OR of 0.68 (95% CI, 0.63-0.73) and 0.77 (95% CI, 0.69-0.87) for women on estrogen alone. Similar results were found for ESCC. For GAC, combination resulted in an aOR of 0.85 (95% CI, 0.80-0.89) and 0.88 (95% CI, 0.81-0.97) in estrogen only therapy respectively.

“Our results reinforce the concept that estrogenic signaling may influence tumor development in the upper GI tract,” said Wocalewski. “Understanding these mechanisms could help identify at-risk populations and inform prevention strategies,” she added, noting that, “hormonal effects on epithelial tight junctions and nitric oxide synthesis in the gastrointestinal tract” would have an influence on smooth muscle cells.

 

Link Between Hormones and GI Pathology

Commenting on the study for GI & Hepatology News, Jan Bornschein, MD, University of Oxford, UK, who was not involved in the research, said the results are “highly relevant.” 

“We’ve seen for a long time a link between hormones and GI pathology, however, it has been poorly investigated and the whole mechanisms are not understood, so it’s welcome that this group is moving forward and investigating this in a structured way,” he said.

Another delegate cautioned that MHT was associated with a risk for other non- gastrointestinal cancers. “I think it’s extremely important, because there are data on associations [of MHT] with breast cancer and also endometrial cancer. It’s good to see that it may help and reduce this cancer, but we have to be really careful about the others.”

Wocalewski reports no relevant conflicts of interest. Bornschein has no disclosures relevant to this study. The study was funded by Karolinska Institutet and supported by national cancer and prescription registry data from Denmark, Finland, Iceland, Norway, and Sweden.

 

A version of this article appeared on Medscape.com.

DENVER – Standard intact protein formulas (SPFs) significantly increased the risk for gastrointestinal complications in premature infants compared to extensively hydrolyzed formulas (eHFs), according to new data presented at the American Academy of Pediatrics (AAP) 2025 National Conference & Exhibition.

Necrotizing enterocolitis (NEC) can affect the intestinal wall of neonates, with potentially life-threatening results. The inflammatory condition is characterized by feeding intolerance, rectal bleeding, and bowel perforations, said presenting author Puja Kulkarni, medical student at California Northstate University College of Medicine, Elk Grove, California, and colleagues.

The etiology of NEC remains unclear, but previous research suggests that formula feeding may play a role, the researchers said. “NEC remains a leading cause of morbidity and mortality in premature infants, yet there is still no clear consensus on the optimal feeding strategy to reduce risk,” Kulkarni said in an interview with GI & Hepatology News.

Most hospital guidelines call for solely using SPFs in NICUs, especially in cases where maternal breast milk is not available, said Kulkarni. Therefore, “it was critical to investigate whether different types of formula, such as extensively hydrolyzed formula, could influence the incidence of NEC,” she said.

Kulkarni and colleagues conducted a literature search and identified three randomized, controlled trials that compared eHFs to SPFs in a study population of 1180 premature infants.

Overall, infants who received SPFs had a significantly greater risk for both NEC and feeding intolerance than those who received eHFs, with odds ratios of 2.54 and 2.87, respectively, and these associations remained after a sensitivity analysis. 

Other research, such as the German Infant Nutritional Intervention (GINI) study, has shown similar results regarding the effect of formula type on childhood pathologies, Kulkarni noted. The GINI study showed that HFs can help prevent the development of allergic diseases in children with a family history of allergies, she said.

The results of the current analysis suggest a significantly increased risk for NEC, as well as feeding intolerance, which can be a precursor to NEC, in premature infants fed SPFs compared to those fed eHFs, said Kulkarni. “If validated by further research, this could lead to changes in NICU feeding protocols, especially in situations where donor breast milk is not available. Clinicians may want to consider the type of protein in formula as an important factor in NEC prevention,” she said. The current findings support the need for more research into the effects of formula throughout the infant and childhood years.

Additional studies are needed to validate the findings in larger, multicenter cohorts to ensure generalizability, especially in the US, where current guidelines favor SPFs based on limited data, said Kulkarni. Much of the research in the US has been conducted by the formula companies themselves, and she and her colleagues took this risk for bias into account in their meta-analysis.

 

Younger Babies at Greater Risk

Documented rates of NEC have remained stable or decreased slightly over the past 20 years, which supports the need for research on prevention and early identification, as well as effective medical treatment, said Catherine Haut, DNP, CPNP-AC/PC, in an interview.

“With improved neonatal intensive care, younger neonates are surviving, but these babies also have a higher risk of development of NEC,” said Haut, director of nursing research and evidence-based practice at Nemours Children’s Health, Delaware, New Jersey, who was not involved in the study.

“Historically, NEC has been related to feeding, among other variables, but the use of more specific or standardized feeding methods including increased use of human milk in very low-birth weight infants has resulted in better outcomes,” she said.

The finding from the current meta-analysis that the use of SPFs poses a higher risk for NEC than the use of eHFs was not unexpected, Haut told GI & Hepatology News. Some infants are allergic to cow’s milk, and replacing this type of formula with eHF is the recommended treatment as these formulas incorporate proteins which are more easily digested, she said.

Systematic reviews and meta-analyses are considered high levels of evidence, and the current study’s documentation of the benefits of eHF could help decrease the rate of NEC in premature infants, Haut said. “Despite a higher cost associated with eHF, in formula-fed preterm neonates, there would be benefit to using eHF vs risk of standard protein formulas,” she said.

However, the current study represents a very small population compared to the total number of infants born at less than 37 weeks’ gestation, which is reported to be 10% of all newborns in the US each year, Haut noted.

Additional large studies, including randomized control trials, are needed to further document the effects of using eHF in very young premature infants and potentially help reduce the incidence of NEC in this population, she said.

The study received no outside funding. The researchers and Haut had no financial conflicts to disclose.

 

A version of this article appeared on Medscape.com.

DENVER – Standard intact protein formulas (SPFs) significantly increased the risk for gastrointestinal complications in premature infants compared to extensively hydrolyzed formulas (eHFs), according to new data presented at the American Academy of Pediatrics (AAP) 2025 National Conference & Exhibition.

Necrotizing enterocolitis (NEC) can affect the intestinal wall of neonates, with potentially life-threatening results. The inflammatory condition is characterized by feeding intolerance, rectal bleeding, and bowel perforations, said presenting author Puja Kulkarni, medical student at California Northstate University College of Medicine, Elk Grove, California, and colleagues.

The etiology of NEC remains unclear, but previous research suggests that formula feeding may play a role, the researchers said. “NEC remains a leading cause of morbidity and mortality in premature infants, yet there is still no clear consensus on the optimal feeding strategy to reduce risk,” Kulkarni said in an interview with GI & Hepatology News.

Most hospital guidelines call for solely using SPFs in NICUs, especially in cases where maternal breast milk is not available, said Kulkarni. Therefore, “it was critical to investigate whether different types of formula, such as extensively hydrolyzed formula, could influence the incidence of NEC,” she said.

Kulkarni and colleagues conducted a literature search and identified three randomized, controlled trials that compared eHFs to SPFs in a study population of 1180 premature infants.

Overall, infants who received SPFs had a significantly greater risk for both NEC and feeding intolerance than those who received eHFs, with odds ratios of 2.54 and 2.87, respectively, and these associations remained after a sensitivity analysis. 

Other research, such as the German Infant Nutritional Intervention (GINI) study, has shown similar results regarding the effect of formula type on childhood pathologies, Kulkarni noted. The GINI study showed that HFs can help prevent the development of allergic diseases in children with a family history of allergies, she said.

The results of the current analysis suggest a significantly increased risk for NEC, as well as feeding intolerance, which can be a precursor to NEC, in premature infants fed SPFs compared to those fed eHFs, said Kulkarni. “If validated by further research, this could lead to changes in NICU feeding protocols, especially in situations where donor breast milk is not available. Clinicians may want to consider the type of protein in formula as an important factor in NEC prevention,” she said. The current findings support the need for more research into the effects of formula throughout the infant and childhood years.

Additional studies are needed to validate the findings in larger, multicenter cohorts to ensure generalizability, especially in the US, where current guidelines favor SPFs based on limited data, said Kulkarni. Much of the research in the US has been conducted by the formula companies themselves, and she and her colleagues took this risk for bias into account in their meta-analysis.

 

Younger Babies at Greater Risk

Documented rates of NEC have remained stable or decreased slightly over the past 20 years, which supports the need for research on prevention and early identification, as well as effective medical treatment, said Catherine Haut, DNP, CPNP-AC/PC, in an interview.

“With improved neonatal intensive care, younger neonates are surviving, but these babies also have a higher risk of development of NEC,” said Haut, director of nursing research and evidence-based practice at Nemours Children’s Health, Delaware, New Jersey, who was not involved in the study.

“Historically, NEC has been related to feeding, among other variables, but the use of more specific or standardized feeding methods including increased use of human milk in very low-birth weight infants has resulted in better outcomes,” she said.

The finding from the current meta-analysis that the use of SPFs poses a higher risk for NEC than the use of eHFs was not unexpected, Haut told GI & Hepatology News. Some infants are allergic to cow’s milk, and replacing this type of formula with eHF is the recommended treatment as these formulas incorporate proteins which are more easily digested, she said.

Systematic reviews and meta-analyses are considered high levels of evidence, and the current study’s documentation of the benefits of eHF could help decrease the rate of NEC in premature infants, Haut said. “Despite a higher cost associated with eHF, in formula-fed preterm neonates, there would be benefit to using eHF vs risk of standard protein formulas,” she said.

However, the current study represents a very small population compared to the total number of infants born at less than 37 weeks’ gestation, which is reported to be 10% of all newborns in the US each year, Haut noted.

Additional large studies, including randomized control trials, are needed to further document the effects of using eHF in very young premature infants and potentially help reduce the incidence of NEC in this population, she said.

The study received no outside funding. The researchers and Haut had no financial conflicts to disclose.

 

A version of this article appeared on Medscape.com.

DENVER – Standard intact protein formulas (SPFs) significantly increased the risk for gastrointestinal complications in premature infants compared to extensively hydrolyzed formulas (eHFs), according to new data presented at the American Academy of Pediatrics (AAP) 2025 National Conference & Exhibition.

Necrotizing enterocolitis (NEC) can affect the intestinal wall of neonates, with potentially life-threatening results. The inflammatory condition is characterized by feeding intolerance, rectal bleeding, and bowel perforations, said presenting author Puja Kulkarni, medical student at California Northstate University College of Medicine, Elk Grove, California, and colleagues.

The etiology of NEC remains unclear, but previous research suggests that formula feeding may play a role, the researchers said. “NEC remains a leading cause of morbidity and mortality in premature infants, yet there is still no clear consensus on the optimal feeding strategy to reduce risk,” Kulkarni said in an interview with GI & Hepatology News.

Most hospital guidelines call for solely using SPFs in NICUs, especially in cases where maternal breast milk is not available, said Kulkarni. Therefore, “it was critical to investigate whether different types of formula, such as extensively hydrolyzed formula, could influence the incidence of NEC,” she said.

Kulkarni and colleagues conducted a literature search and identified three randomized, controlled trials that compared eHFs to SPFs in a study population of 1180 premature infants.

Overall, infants who received SPFs had a significantly greater risk for both NEC and feeding intolerance than those who received eHFs, with odds ratios of 2.54 and 2.87, respectively, and these associations remained after a sensitivity analysis. 

Other research, such as the German Infant Nutritional Intervention (GINI) study, has shown similar results regarding the effect of formula type on childhood pathologies, Kulkarni noted. The GINI study showed that HFs can help prevent the development of allergic diseases in children with a family history of allergies, she said.

The results of the current analysis suggest a significantly increased risk for NEC, as well as feeding intolerance, which can be a precursor to NEC, in premature infants fed SPFs compared to those fed eHFs, said Kulkarni. “If validated by further research, this could lead to changes in NICU feeding protocols, especially in situations where donor breast milk is not available. Clinicians may want to consider the type of protein in formula as an important factor in NEC prevention,” she said. The current findings support the need for more research into the effects of formula throughout the infant and childhood years.

Additional studies are needed to validate the findings in larger, multicenter cohorts to ensure generalizability, especially in the US, where current guidelines favor SPFs based on limited data, said Kulkarni. Much of the research in the US has been conducted by the formula companies themselves, and she and her colleagues took this risk for bias into account in their meta-analysis.

 

Younger Babies at Greater Risk

Documented rates of NEC have remained stable or decreased slightly over the past 20 years, which supports the need for research on prevention and early identification, as well as effective medical treatment, said Catherine Haut, DNP, CPNP-AC/PC, in an interview.

“With improved neonatal intensive care, younger neonates are surviving, but these babies also have a higher risk of development of NEC,” said Haut, director of nursing research and evidence-based practice at Nemours Children’s Health, Delaware, New Jersey, who was not involved in the study.

“Historically, NEC has been related to feeding, among other variables, but the use of more specific or standardized feeding methods including increased use of human milk in very low-birth weight infants has resulted in better outcomes,” she said.

The finding from the current meta-analysis that the use of SPFs poses a higher risk for NEC than the use of eHFs was not unexpected, Haut told GI & Hepatology News. Some infants are allergic to cow’s milk, and replacing this type of formula with eHF is the recommended treatment as these formulas incorporate proteins which are more easily digested, she said.

Systematic reviews and meta-analyses are considered high levels of evidence, and the current study’s documentation of the benefits of eHF could help decrease the rate of NEC in premature infants, Haut said. “Despite a higher cost associated with eHF, in formula-fed preterm neonates, there would be benefit to using eHF vs risk of standard protein formulas,” she said.

However, the current study represents a very small population compared to the total number of infants born at less than 37 weeks’ gestation, which is reported to be 10% of all newborns in the US each year, Haut noted.

Additional large studies, including randomized control trials, are needed to further document the effects of using eHF in very young premature infants and potentially help reduce the incidence of NEC in this population, she said.

The study received no outside funding. The researchers and Haut had no financial conflicts to disclose.

 

A version of this article appeared on Medscape.com.