Key clinical point: No single first-line treatment for advanced hepatocellular carcinoma demonstrated superior outcomes across all measures, therefore treatment should be based on individual goals.

Major finding: Lenvatinib ranked highest for overall response rate for patients with advanced/unresectable HCC, followed by atezolizumab plus bevacizumab and nivolumab. For progression-free survival, the top-ranked treatments was atezolizumab + bevacizumab, followed by lenvatinib.

Study details: The data come from a meta-analysis of 27 randomized, controlled trials of first-line therapies for hepatocellular carcinoma. The treatments compared in the studies were Treatments compared were atezolizumab plus bevacizumab, brivanib, donafenib, dovitinib, FOLFOX4, lenvatinib, linifanib, nintedanib, nivolumab, sorafenib, sunitinib, vandetanib, 11 sorafenib combination therapies, and 3 other combination therapies. 

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.  

Source: Han Y et al. World J. Gastroenterol. 2021 May 21. doi: 10.3748/wjg.v27.i19.2415.

Key clinical point: No single first-line treatment for advanced hepatocellular carcinoma demonstrated superior outcomes across all measures, therefore treatment should be based on individual goals.

Major finding: Lenvatinib ranked highest for overall response rate for patients with advanced/unresectable HCC, followed by atezolizumab plus bevacizumab and nivolumab. For progression-free survival, the top-ranked treatments was atezolizumab + bevacizumab, followed by lenvatinib.

Study details: The data come from a meta-analysis of 27 randomized, controlled trials of first-line therapies for hepatocellular carcinoma. The treatments compared in the studies were Treatments compared were atezolizumab plus bevacizumab, brivanib, donafenib, dovitinib, FOLFOX4, lenvatinib, linifanib, nintedanib, nivolumab, sorafenib, sunitinib, vandetanib, 11 sorafenib combination therapies, and 3 other combination therapies. 

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.  

Source: Han Y et al. World J. Gastroenterol. 2021 May 21. doi: 10.3748/wjg.v27.i19.2415.

Key clinical point: No single first-line treatment for advanced hepatocellular carcinoma demonstrated superior outcomes across all measures, therefore treatment should be based on individual goals.

Major finding: Lenvatinib ranked highest for overall response rate for patients with advanced/unresectable HCC, followed by atezolizumab plus bevacizumab and nivolumab. For progression-free survival, the top-ranked treatments was atezolizumab + bevacizumab, followed by lenvatinib.

Study details: The data come from a meta-analysis of 27 randomized, controlled trials of first-line therapies for hepatocellular carcinoma. The treatments compared in the studies were Treatments compared were atezolizumab plus bevacizumab, brivanib, donafenib, dovitinib, FOLFOX4, lenvatinib, linifanib, nintedanib, nivolumab, sorafenib, sunitinib, vandetanib, 11 sorafenib combination therapies, and 3 other combination therapies. 

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.  

Source: Han Y et al. World J. Gastroenterol. 2021 May 21. doi: 10.3748/wjg.v27.i19.2415.

Key clinical point: The EZ albumin-bilirubin (ALBI) score was significantly correlated with the original and more complex ALBI score as a biomarker of liver injury.

Major finding: The correlation coefficient of the EZ-ALBI score with the standard ALBI score was 0.965 (P < 0.001). In multivariate analysis, factors including EZ-ALBI grade 2 and 3 were independently associated with increased mortality.

Study details: The data come from 3,794 patients newly diagnosed with HCC who were prospectively enrolled in the study and later analyzed.

Disclosures: The study was supported by the Taipei Veterans General Hospital. The researchers had no financial conflicts to disclose.  

Source: Ho S-Y et al. Hepatol Res. 2021 May 26. doi:10.1111/hepr.13671.

Key clinical point: The EZ albumin-bilirubin (ALBI) score was significantly correlated with the original and more complex ALBI score as a biomarker of liver injury.

Major finding: The correlation coefficient of the EZ-ALBI score with the standard ALBI score was 0.965 (P < 0.001). In multivariate analysis, factors including EZ-ALBI grade 2 and 3 were independently associated with increased mortality.

Study details: The data come from 3,794 patients newly diagnosed with HCC who were prospectively enrolled in the study and later analyzed.

Disclosures: The study was supported by the Taipei Veterans General Hospital. The researchers had no financial conflicts to disclose.  

Source: Ho S-Y et al. Hepatol Res. 2021 May 26. doi:10.1111/hepr.13671.

Key clinical point: The EZ albumin-bilirubin (ALBI) score was significantly correlated with the original and more complex ALBI score as a biomarker of liver injury.

Major finding: The correlation coefficient of the EZ-ALBI score with the standard ALBI score was 0.965 (P < 0.001). In multivariate analysis, factors including EZ-ALBI grade 2 and 3 were independently associated with increased mortality.

Study details: The data come from 3,794 patients newly diagnosed with HCC who were prospectively enrolled in the study and later analyzed.

Disclosures: The study was supported by the Taipei Veterans General Hospital. The researchers had no financial conflicts to disclose.  

Source: Ho S-Y et al. Hepatol Res. 2021 May 26. doi:10.1111/hepr.13671.

Key clinical point: Over a median follow-up of 36.7 months, safety and efficacy based on complications and rates of overall survival were not significantly different between hepatocellular carcinoma patients treated with radiofrequency ablation (RFA) and those treated with microwave ablation (MWA).

Major finding: Cumulative overall survival rates at 1, 3, and 5 years were 97.9%, 92.3%, and 80.6%, respectively, for MWA patients and 96.4%, 87.4%, and 78.2%, respectively, for RFA patients (P = 0.450).  Major complication rates also were similar between the two groups (3.3% vs. 3.9%).

Study details: The data come from a retrospective study of 201 consecutive adult patients with hepatocellular carcinoma who underwent either radiofrequency ablation (150 patients) or microwave ablation (51 patients) at a single center between January 2012 and December 2016.

Disclosures: The study was supported by the Guangzhou Science and Technology Program and the Innovative Research Group Project of the National Natural Science Foundation of China.  The researchers had no financial conflicts to disclose.  

Source: Han X et al. Abdom Radiol. 2021 May 25. doi: 10.1007/s00261-021-03105-9.

Key clinical point: Over a median follow-up of 36.7 months, safety and efficacy based on complications and rates of overall survival were not significantly different between hepatocellular carcinoma patients treated with radiofrequency ablation (RFA) and those treated with microwave ablation (MWA).

Major finding: Cumulative overall survival rates at 1, 3, and 5 years were 97.9%, 92.3%, and 80.6%, respectively, for MWA patients and 96.4%, 87.4%, and 78.2%, respectively, for RFA patients (P = 0.450).  Major complication rates also were similar between the two groups (3.3% vs. 3.9%).

Study details: The data come from a retrospective study of 201 consecutive adult patients with hepatocellular carcinoma who underwent either radiofrequency ablation (150 patients) or microwave ablation (51 patients) at a single center between January 2012 and December 2016.

Disclosures: The study was supported by the Guangzhou Science and Technology Program and the Innovative Research Group Project of the National Natural Science Foundation of China.  The researchers had no financial conflicts to disclose.  

Source: Han X et al. Abdom Radiol. 2021 May 25. doi: 10.1007/s00261-021-03105-9.

Key clinical point: Over a median follow-up of 36.7 months, safety and efficacy based on complications and rates of overall survival were not significantly different between hepatocellular carcinoma patients treated with radiofrequency ablation (RFA) and those treated with microwave ablation (MWA).

Major finding: Cumulative overall survival rates at 1, 3, and 5 years were 97.9%, 92.3%, and 80.6%, respectively, for MWA patients and 96.4%, 87.4%, and 78.2%, respectively, for RFA patients (P = 0.450).  Major complication rates also were similar between the two groups (3.3% vs. 3.9%).

Study details: The data come from a retrospective study of 201 consecutive adult patients with hepatocellular carcinoma who underwent either radiofrequency ablation (150 patients) or microwave ablation (51 patients) at a single center between January 2012 and December 2016.

Disclosures: The study was supported by the Guangzhou Science and Technology Program and the Innovative Research Group Project of the National Natural Science Foundation of China.  The researchers had no financial conflicts to disclose.  

Source: Han X et al. Abdom Radiol. 2021 May 25. doi: 10.1007/s00261-021-03105-9.

First is an article from Elshaarawy O et al. who looked at preoperative and postoperative models to evaluate postresection survival. Between December 2010 and January 2017, 120 patients who underwent resection with curative intent, were analyzed for survival, liver decompensation, and posthepatectomy liver failure (PHLF). It will come as no surprise that HCC recurrence following resection adversely affected survival (hazard ratio (HR) = 11.67, 95%CI: 4.19-32.52, P < 0.001). Also affecting survival were the preoperative MELD score [HR = 1.37, 95%CI: 1.16-1.62, P < 0.001] and grades A through C of the PHLF score. Significant independent predictors of postoperative liver decompensation were the preoperative MELD score >10 [odds ratio (OR) = 2.7, 95%CI: 1.2-5.7, P = 0.013], tumor diameter >5 cm (OR = 5.4, 95%CI: 2-14.8, P = 0.001) and duration of hospital stay (6. 8 days vs 11.26 days; OR = 2.5, 95%CI: 1.5-4.2, P = 0.001).

Next, Lei GY et al. undertook a retrospective study of 244 patients with HCC who underwent hepatic resection with curative intent between January 200 and December 2017. They found that the overall postoperative 90-day mortality rate for HCC patients after hepatic resection was 5.3%. Significant predictors of mortality Child-Pugh score (p < 0.001), intraoperative blood loss (P = 0.013), the 50-50 criteria for PHLF (P < 0.001) on postoperative day 5, and peak serum bilirubin >119 µmol/L (P = 0.007) on postoperative day 3. In these patients, the overall postoperative 90-day mortality rate for HCC patients after hepatic resection was 5.3%.

Taken together, these studies confirm that underlying liver function both before and after surgery is a key predictor of how well a patient is likely to do after curative-intent surgery. Excellent multidisciplinary care remains important for patient well-being.

Finally, for patients who are not candidates for liver resection, Han X et al. evaluated the efficacy of radiofrequency ablation (RFA) and microwave ablation (MWA) in a retrospective study of 201 consecutive patients whose tumors were within Milan criteria, but were in challenging locations for resection. RFA was performed in 150 patients, while 51 patients underwent MWA between January 2012 and December 2016.  Median follow-up was 36.7 months. Cumulative overall survival rates at 1, 3, and 5 years were 97.9%, 92.3%, and 80.6%, respectively, for MWA patients and 96.4%, 87.4%, and 78.2%, respectively, for RFA patients (P = 0.450).  Major complication rates also were similar between the two groups (3.3% vs. 3.9%). The authors concluded that both procedures are equally safe and effective in patients with HCC.

First is an article from Elshaarawy O et al. who looked at preoperative and postoperative models to evaluate postresection survival. Between December 2010 and January 2017, 120 patients who underwent resection with curative intent, were analyzed for survival, liver decompensation, and posthepatectomy liver failure (PHLF). It will come as no surprise that HCC recurrence following resection adversely affected survival (hazard ratio (HR) = 11.67, 95%CI: 4.19-32.52, P < 0.001). Also affecting survival were the preoperative MELD score [HR = 1.37, 95%CI: 1.16-1.62, P < 0.001] and grades A through C of the PHLF score. Significant independent predictors of postoperative liver decompensation were the preoperative MELD score >10 [odds ratio (OR) = 2.7, 95%CI: 1.2-5.7, P = 0.013], tumor diameter >5 cm (OR = 5.4, 95%CI: 2-14.8, P = 0.001) and duration of hospital stay (6. 8 days vs 11.26 days; OR = 2.5, 95%CI: 1.5-4.2, P = 0.001).

Next, Lei GY et al. undertook a retrospective study of 244 patients with HCC who underwent hepatic resection with curative intent between January 200 and December 2017. They found that the overall postoperative 90-day mortality rate for HCC patients after hepatic resection was 5.3%. Significant predictors of mortality Child-Pugh score (p < 0.001), intraoperative blood loss (P = 0.013), the 50-50 criteria for PHLF (P < 0.001) on postoperative day 5, and peak serum bilirubin >119 µmol/L (P = 0.007) on postoperative day 3. In these patients, the overall postoperative 90-day mortality rate for HCC patients after hepatic resection was 5.3%.

Taken together, these studies confirm that underlying liver function both before and after surgery is a key predictor of how well a patient is likely to do after curative-intent surgery. Excellent multidisciplinary care remains important for patient well-being.

Finally, for patients who are not candidates for liver resection, Han X et al. evaluated the efficacy of radiofrequency ablation (RFA) and microwave ablation (MWA) in a retrospective study of 201 consecutive patients whose tumors were within Milan criteria, but were in challenging locations for resection. RFA was performed in 150 patients, while 51 patients underwent MWA between January 2012 and December 2016.  Median follow-up was 36.7 months. Cumulative overall survival rates at 1, 3, and 5 years were 97.9%, 92.3%, and 80.6%, respectively, for MWA patients and 96.4%, 87.4%, and 78.2%, respectively, for RFA patients (P = 0.450).  Major complication rates also were similar between the two groups (3.3% vs. 3.9%). The authors concluded that both procedures are equally safe and effective in patients with HCC.

First is an article from Elshaarawy O et al. who looked at preoperative and postoperative models to evaluate postresection survival. Between December 2010 and January 2017, 120 patients who underwent resection with curative intent, were analyzed for survival, liver decompensation, and posthepatectomy liver failure (PHLF). It will come as no surprise that HCC recurrence following resection adversely affected survival (hazard ratio (HR) = 11.67, 95%CI: 4.19-32.52, P < 0.001). Also affecting survival were the preoperative MELD score [HR = 1.37, 95%CI: 1.16-1.62, P < 0.001] and grades A through C of the PHLF score. Significant independent predictors of postoperative liver decompensation were the preoperative MELD score >10 [odds ratio (OR) = 2.7, 95%CI: 1.2-5.7, P = 0.013], tumor diameter >5 cm (OR = 5.4, 95%CI: 2-14.8, P = 0.001) and duration of hospital stay (6. 8 days vs 11.26 days; OR = 2.5, 95%CI: 1.5-4.2, P = 0.001).

Next, Lei GY et al. undertook a retrospective study of 244 patients with HCC who underwent hepatic resection with curative intent between January 200 and December 2017. They found that the overall postoperative 90-day mortality rate for HCC patients after hepatic resection was 5.3%. Significant predictors of mortality Child-Pugh score (p < 0.001), intraoperative blood loss (P = 0.013), the 50-50 criteria for PHLF (P < 0.001) on postoperative day 5, and peak serum bilirubin >119 µmol/L (P = 0.007) on postoperative day 3. In these patients, the overall postoperative 90-day mortality rate for HCC patients after hepatic resection was 5.3%.

Taken together, these studies confirm that underlying liver function both before and after surgery is a key predictor of how well a patient is likely to do after curative-intent surgery. Excellent multidisciplinary care remains important for patient well-being.

Finally, for patients who are not candidates for liver resection, Han X et al. evaluated the efficacy of radiofrequency ablation (RFA) and microwave ablation (MWA) in a retrospective study of 201 consecutive patients whose tumors were within Milan criteria, but were in challenging locations for resection. RFA was performed in 150 patients, while 51 patients underwent MWA between January 2012 and December 2016.  Median follow-up was 36.7 months. Cumulative overall survival rates at 1, 3, and 5 years were 97.9%, 92.3%, and 80.6%, respectively, for MWA patients and 96.4%, 87.4%, and 78.2%, respectively, for RFA patients (P = 0.450).  Major complication rates also were similar between the two groups (3.3% vs. 3.9%). The authors concluded that both procedures are equally safe and effective in patients with HCC.

Reassuring news for women who receive a diagnosis of breast cancer during pregnancy: Pregnancy-induced alterations in the pharmacokinetics of chemotherapy do not appear to compromise outcomes for the mother.

That’s according to investigators who reviewed registry data on 662 pregnant women and 2,081 nonpregnant women with a diagnosis of breast cancer. After a median follow-up of 66 months, there were no significant differences in either disease-free survival (DFS) or overall survival (OS), and women who received more than 60% of their chemotherapy doses during pregnancy had survival comparable to that of nonpregnant women, reported Frédéric Amant, MD, PhD, of University Hospitals Leuven (Belgium).

“These results support initiation of chemotherapy for breast cancer during pregnancy where indicated for oncological reasons,” they reported in a poster discussion session at the American Society of Clinical Oncology annual meeting. (Abstract 515).

Although in general a diagnosis of breast cancer during pregnancy does not appear to affect the mother’s prognosis when standard therapy is used, “caution is warranted as gestational changes in pharmacokinetics with respect to the distribution, metabolism, and excretion of drugs may lead to reduced chemotherapy concentration in pregnant patients,” the authors wrote.

To get a better picture of the prognosis for women diagnosed with breast cancer during pregnancy, the investigators created a cohort of patients from two multicenter registries: the International Network of Cancer, Infertility, and Pregnancy and the German Breast Group. Both registries collect data retrospectively and prospectively,

They used propensity scoring to smooth out differences in the baseline characteristics of pregnant women and nonpregnant controls.

The median age at diagnosis was 34 year for pregnant women, and 38 years for controls. Pregnant women were more likely than were controls to have stage II disease (60.1% vs. 56, 1%, P = .035), grade 3 tumors (74% vs. 62.2%, P < .001), hormone receptor–negative breast tumors (48.4% vs. 30%), and triple-negative breast cancer (38.9% vs. 26.9%, P < .001).

In Cox proportional hazard regression analysis controlling for age, stage, grade, hormone receptor status, HER2 status and histology, there were no significant differences between pregnant women and controls in either DFS (hazard ratio [HR] 1.02, P = .83) or OS (HR 1.08, P = .57).

As noted before, a subgroup analysis of 339 women who received more than 60% of their assigned chemotherapy doses during pregnancy also showed that survival was not significantly different from that of nonpregnant women (HR for DFS 0,71, P = .13; HR for OS 0.85, P = .39).
 

Termination does not benefit the mother

“Thanks to the important work of Dr. Amant in the INCIP [International Network on Cancer, Infertility, and Pregnancy] network and others around the world, we now have sufficient data to know that it’s safe to treat breast cancer during pregnancy, and that the prognosis of breast cancer during pregnancy is comparable to nonpregnant controls if we adjust for certain characteristics such as age and others,” said Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, Portugal, the invited discussant.

­­“With this and other studies, we can come to the conclusion that pregnancy-induced alterations in the chemotherapy concentration due to altered pharmacokinetics does not seem to affect maternal prognosis, and therefore we should initiate treatment of breast cancer during wherever it’s indicated for oncological reasons, knowing that you can only use chemotherapy during the second or third trimester,” she said.

Dr. Cardoso emphasized that breast cancer during pregnancy is a rare situation requiring that treatment be given in a specialized center by an experienced multidisciplinary team, and that interrupting the pregnancy does not improve the mother’s prognosis.

“We have to spread the word to all health professionals who come across these women to stop advising them to immediately terminate pregnancy. For the children, the most important take-home message is avoid prematurely delivery,” she said.

Treatment for women with a diagnosis of breast cancer during pregnancy should be similar to that for nonpregnant women, with the exception of endocrine therapy and anti-HER2 agents, which should be withheld until after delivery, she added.

The study was supported by the European Research Council, Research Foundation Flanders, and Kom op tegen kanker (Stand Up to Cancer). Dr. Amant disclosed a consulting or advisory role for AstraZeneca and Clovis Oncology. Dr. Cardoso disclosed consulting or advisory roles and travel support from multiple companies.

Reassuring news for women who receive a diagnosis of breast cancer during pregnancy: Pregnancy-induced alterations in the pharmacokinetics of chemotherapy do not appear to compromise outcomes for the mother.

That’s according to investigators who reviewed registry data on 662 pregnant women and 2,081 nonpregnant women with a diagnosis of breast cancer. After a median follow-up of 66 months, there were no significant differences in either disease-free survival (DFS) or overall survival (OS), and women who received more than 60% of their chemotherapy doses during pregnancy had survival comparable to that of nonpregnant women, reported Frédéric Amant, MD, PhD, of University Hospitals Leuven (Belgium).

“These results support initiation of chemotherapy for breast cancer during pregnancy where indicated for oncological reasons,” they reported in a poster discussion session at the American Society of Clinical Oncology annual meeting. (Abstract 515).

Although in general a diagnosis of breast cancer during pregnancy does not appear to affect the mother’s prognosis when standard therapy is used, “caution is warranted as gestational changes in pharmacokinetics with respect to the distribution, metabolism, and excretion of drugs may lead to reduced chemotherapy concentration in pregnant patients,” the authors wrote.

To get a better picture of the prognosis for women diagnosed with breast cancer during pregnancy, the investigators created a cohort of patients from two multicenter registries: the International Network of Cancer, Infertility, and Pregnancy and the German Breast Group. Both registries collect data retrospectively and prospectively,

They used propensity scoring to smooth out differences in the baseline characteristics of pregnant women and nonpregnant controls.

The median age at diagnosis was 34 year for pregnant women, and 38 years for controls. Pregnant women were more likely than were controls to have stage II disease (60.1% vs. 56, 1%, P = .035), grade 3 tumors (74% vs. 62.2%, P < .001), hormone receptor–negative breast tumors (48.4% vs. 30%), and triple-negative breast cancer (38.9% vs. 26.9%, P < .001).

In Cox proportional hazard regression analysis controlling for age, stage, grade, hormone receptor status, HER2 status and histology, there were no significant differences between pregnant women and controls in either DFS (hazard ratio [HR] 1.02, P = .83) or OS (HR 1.08, P = .57).

As noted before, a subgroup analysis of 339 women who received more than 60% of their assigned chemotherapy doses during pregnancy also showed that survival was not significantly different from that of nonpregnant women (HR for DFS 0,71, P = .13; HR for OS 0.85, P = .39).
 

Termination does not benefit the mother

“Thanks to the important work of Dr. Amant in the INCIP [International Network on Cancer, Infertility, and Pregnancy] network and others around the world, we now have sufficient data to know that it’s safe to treat breast cancer during pregnancy, and that the prognosis of breast cancer during pregnancy is comparable to nonpregnant controls if we adjust for certain characteristics such as age and others,” said Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, Portugal, the invited discussant.

­­“With this and other studies, we can come to the conclusion that pregnancy-induced alterations in the chemotherapy concentration due to altered pharmacokinetics does not seem to affect maternal prognosis, and therefore we should initiate treatment of breast cancer during wherever it’s indicated for oncological reasons, knowing that you can only use chemotherapy during the second or third trimester,” she said.

Dr. Cardoso emphasized that breast cancer during pregnancy is a rare situation requiring that treatment be given in a specialized center by an experienced multidisciplinary team, and that interrupting the pregnancy does not improve the mother’s prognosis.

“We have to spread the word to all health professionals who come across these women to stop advising them to immediately terminate pregnancy. For the children, the most important take-home message is avoid prematurely delivery,” she said.

Treatment for women with a diagnosis of breast cancer during pregnancy should be similar to that for nonpregnant women, with the exception of endocrine therapy and anti-HER2 agents, which should be withheld until after delivery, she added.

The study was supported by the European Research Council, Research Foundation Flanders, and Kom op tegen kanker (Stand Up to Cancer). Dr. Amant disclosed a consulting or advisory role for AstraZeneca and Clovis Oncology. Dr. Cardoso disclosed consulting or advisory roles and travel support from multiple companies.

Reassuring news for women who receive a diagnosis of breast cancer during pregnancy: Pregnancy-induced alterations in the pharmacokinetics of chemotherapy do not appear to compromise outcomes for the mother.

That’s according to investigators who reviewed registry data on 662 pregnant women and 2,081 nonpregnant women with a diagnosis of breast cancer. After a median follow-up of 66 months, there were no significant differences in either disease-free survival (DFS) or overall survival (OS), and women who received more than 60% of their chemotherapy doses during pregnancy had survival comparable to that of nonpregnant women, reported Frédéric Amant, MD, PhD, of University Hospitals Leuven (Belgium).

“These results support initiation of chemotherapy for breast cancer during pregnancy where indicated for oncological reasons,” they reported in a poster discussion session at the American Society of Clinical Oncology annual meeting. (Abstract 515).

Although in general a diagnosis of breast cancer during pregnancy does not appear to affect the mother’s prognosis when standard therapy is used, “caution is warranted as gestational changes in pharmacokinetics with respect to the distribution, metabolism, and excretion of drugs may lead to reduced chemotherapy concentration in pregnant patients,” the authors wrote.

To get a better picture of the prognosis for women diagnosed with breast cancer during pregnancy, the investigators created a cohort of patients from two multicenter registries: the International Network of Cancer, Infertility, and Pregnancy and the German Breast Group. Both registries collect data retrospectively and prospectively,

They used propensity scoring to smooth out differences in the baseline characteristics of pregnant women and nonpregnant controls.

The median age at diagnosis was 34 year for pregnant women, and 38 years for controls. Pregnant women were more likely than were controls to have stage II disease (60.1% vs. 56, 1%, P = .035), grade 3 tumors (74% vs. 62.2%, P < .001), hormone receptor–negative breast tumors (48.4% vs. 30%), and triple-negative breast cancer (38.9% vs. 26.9%, P < .001).

In Cox proportional hazard regression analysis controlling for age, stage, grade, hormone receptor status, HER2 status and histology, there were no significant differences between pregnant women and controls in either DFS (hazard ratio [HR] 1.02, P = .83) or OS (HR 1.08, P = .57).

As noted before, a subgroup analysis of 339 women who received more than 60% of their assigned chemotherapy doses during pregnancy also showed that survival was not significantly different from that of nonpregnant women (HR for DFS 0,71, P = .13; HR for OS 0.85, P = .39).
 

Termination does not benefit the mother

“Thanks to the important work of Dr. Amant in the INCIP [International Network on Cancer, Infertility, and Pregnancy] network and others around the world, we now have sufficient data to know that it’s safe to treat breast cancer during pregnancy, and that the prognosis of breast cancer during pregnancy is comparable to nonpregnant controls if we adjust for certain characteristics such as age and others,” said Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, Portugal, the invited discussant.

­­“With this and other studies, we can come to the conclusion that pregnancy-induced alterations in the chemotherapy concentration due to altered pharmacokinetics does not seem to affect maternal prognosis, and therefore we should initiate treatment of breast cancer during wherever it’s indicated for oncological reasons, knowing that you can only use chemotherapy during the second or third trimester,” she said.

Dr. Cardoso emphasized that breast cancer during pregnancy is a rare situation requiring that treatment be given in a specialized center by an experienced multidisciplinary team, and that interrupting the pregnancy does not improve the mother’s prognosis.

“We have to spread the word to all health professionals who come across these women to stop advising them to immediately terminate pregnancy. For the children, the most important take-home message is avoid prematurely delivery,” she said.

Treatment for women with a diagnosis of breast cancer during pregnancy should be similar to that for nonpregnant women, with the exception of endocrine therapy and anti-HER2 agents, which should be withheld until after delivery, she added.

The study was supported by the European Research Council, Research Foundation Flanders, and Kom op tegen kanker (Stand Up to Cancer). Dr. Amant disclosed a consulting or advisory role for AstraZeneca and Clovis Oncology. Dr. Cardoso disclosed consulting or advisory roles and travel support from multiple companies.

Chemotherapy and local excision led to organ preservation in over half of early-stage rectal cancer patients in a small study, but follow-up was only a median of 15.4 months.

Even so, “we believe that subsequent trials ... are warranted,” said lead investigator Hagen F. Kennecke, MD, medical director of GI oncology at Providence Cancer Institute, Portland, Ore., who presented the findings at the American Society of Clinical Oncology annual meeting.

“The results are quite promising,” said study discussant Karyn Stitzenberg, MD, a surgical oncologist at the University of North Carolina, Chapel Hill.

“The reported organ preservation rates of 57% to 79% compare favorably with the rates previously demonstrated in studies of neoadjuvant chemoradiation followed by local excision,” but longer-term follow up is needed “to know the true organ preservation rate,” she said.

Organ preservation – sparing the rectum during treatment – is a hot topic in rectal cancer. Total mesorectal excision (TME) is still the go-to option, but it’s fraught with bad GI, urinary, sexual, and other complications for patients. “Consequently, the concept of organ preservation ... is very appealing,” Dr. Stitzenberg explained.

The chemoradiation/local excision approach she referenced is gaining traction as an alternative, but the radiation component is itself associated with substantial short- and long-term problems, including sphincter dysfunction and wound healing complications.

The goal of Dr. Kennecke’s study, dubbed NEO [Neoadjuvant, Excision, Observation], was to see if the radiation could be left out altogether.

Recruited at eight centers in Canada and one in the United States, the 58 subjects had clinical stage T1-T3 A/B node-negative tumors with no pathologic high-risk features.

They received neoadjuvant FOLFOX (six cycles in 32 patients, 91% completion rate) or CAPOX (four cycles in 26 patients, 89% completion); 56 of the 58 subjects then went on to transanal endoscopic tumor excision; one of the other two patients wasn’t eligible because of tumor progression and the other one declined.

The 33 patients who were stage T0/T1N0 after treatment were spared organ removal and underwent observation every 3-6 months. TME was recommended for the 23 others who were stage 2 or higher or had nodal metastases following chemotherapy and excision.

The numbers translated to a per-protocol organ preservation rate of 57% over a median follow-up of 15.4 months; when the 13 patients who declined TME were added, the rate climbed to 79%.

Although “organ preservation in rectal cancer is becoming an increasingly promising and realistic option for a subset of patients,” Dr. Stitzenberg said, there are more reasons to be cautious beyond the short follow-up.

“The standard of care treatment for these patients would have been proctectomy ... Most would not have [had] systemic chemotherapy. As a result, the added morbidity of FOLFOX or CAPOX needs to be considered.” The study reported that there were no unexpected toxicities, but “what were the expected toxicities? How many patients experienced grade 3 to 5 complications?” she wondered.

Also, how realistic is it to expect patients to report for surveillance every few months outside of a trial? And how can they best be watched to make sure recurrence is caught “while salvage TME is still feasible? There are many longer-term follow-up questions that remain to be answered,” Dr. Stitzenberg said.

Even with short follow-up, there were two locoregional recurrences across the cohort (3.5%), both treated by TME to R0/1 resection. There were no distant relapses.

Subjects were a median of 67 years old, and over two-thirds were men. The majority had stage 2 disease at baseline. Tumors were well to moderately differentiated nonmucinous rectal adenocarcinomas with a median height of 6 cm.

The work was funded by the Canadian Cancer Trials Group. Dr. Kennecke disclosed relationships with Advanced Accelerator Applications, Ipsen, and Taiho Pharmaceutical. Dr. Stitzenberg had no relevant disclosures.

aotto@mdedge.com

Chemotherapy and local excision led to organ preservation in over half of early-stage rectal cancer patients in a small study, but follow-up was only a median of 15.4 months.

Even so, “we believe that subsequent trials ... are warranted,” said lead investigator Hagen F. Kennecke, MD, medical director of GI oncology at Providence Cancer Institute, Portland, Ore., who presented the findings at the American Society of Clinical Oncology annual meeting.

“The results are quite promising,” said study discussant Karyn Stitzenberg, MD, a surgical oncologist at the University of North Carolina, Chapel Hill.

“The reported organ preservation rates of 57% to 79% compare favorably with the rates previously demonstrated in studies of neoadjuvant chemoradiation followed by local excision,” but longer-term follow up is needed “to know the true organ preservation rate,” she said.

Organ preservation – sparing the rectum during treatment – is a hot topic in rectal cancer. Total mesorectal excision (TME) is still the go-to option, but it’s fraught with bad GI, urinary, sexual, and other complications for patients. “Consequently, the concept of organ preservation ... is very appealing,” Dr. Stitzenberg explained.

The chemoradiation/local excision approach she referenced is gaining traction as an alternative, but the radiation component is itself associated with substantial short- and long-term problems, including sphincter dysfunction and wound healing complications.

The goal of Dr. Kennecke’s study, dubbed NEO [Neoadjuvant, Excision, Observation], was to see if the radiation could be left out altogether.

Recruited at eight centers in Canada and one in the United States, the 58 subjects had clinical stage T1-T3 A/B node-negative tumors with no pathologic high-risk features.

They received neoadjuvant FOLFOX (six cycles in 32 patients, 91% completion rate) or CAPOX (four cycles in 26 patients, 89% completion); 56 of the 58 subjects then went on to transanal endoscopic tumor excision; one of the other two patients wasn’t eligible because of tumor progression and the other one declined.

The 33 patients who were stage T0/T1N0 after treatment were spared organ removal and underwent observation every 3-6 months. TME was recommended for the 23 others who were stage 2 or higher or had nodal metastases following chemotherapy and excision.

The numbers translated to a per-protocol organ preservation rate of 57% over a median follow-up of 15.4 months; when the 13 patients who declined TME were added, the rate climbed to 79%.

Although “organ preservation in rectal cancer is becoming an increasingly promising and realistic option for a subset of patients,” Dr. Stitzenberg said, there are more reasons to be cautious beyond the short follow-up.

“The standard of care treatment for these patients would have been proctectomy ... Most would not have [had] systemic chemotherapy. As a result, the added morbidity of FOLFOX or CAPOX needs to be considered.” The study reported that there were no unexpected toxicities, but “what were the expected toxicities? How many patients experienced grade 3 to 5 complications?” she wondered.

Also, how realistic is it to expect patients to report for surveillance every few months outside of a trial? And how can they best be watched to make sure recurrence is caught “while salvage TME is still feasible? There are many longer-term follow-up questions that remain to be answered,” Dr. Stitzenberg said.

Even with short follow-up, there were two locoregional recurrences across the cohort (3.5%), both treated by TME to R0/1 resection. There were no distant relapses.

Subjects were a median of 67 years old, and over two-thirds were men. The majority had stage 2 disease at baseline. Tumors were well to moderately differentiated nonmucinous rectal adenocarcinomas with a median height of 6 cm.

The work was funded by the Canadian Cancer Trials Group. Dr. Kennecke disclosed relationships with Advanced Accelerator Applications, Ipsen, and Taiho Pharmaceutical. Dr. Stitzenberg had no relevant disclosures.

aotto@mdedge.com

Chemotherapy and local excision led to organ preservation in over half of early-stage rectal cancer patients in a small study, but follow-up was only a median of 15.4 months.

Even so, “we believe that subsequent trials ... are warranted,” said lead investigator Hagen F. Kennecke, MD, medical director of GI oncology at Providence Cancer Institute, Portland, Ore., who presented the findings at the American Society of Clinical Oncology annual meeting.

“The results are quite promising,” said study discussant Karyn Stitzenberg, MD, a surgical oncologist at the University of North Carolina, Chapel Hill.

“The reported organ preservation rates of 57% to 79% compare favorably with the rates previously demonstrated in studies of neoadjuvant chemoradiation followed by local excision,” but longer-term follow up is needed “to know the true organ preservation rate,” she said.

Organ preservation – sparing the rectum during treatment – is a hot topic in rectal cancer. Total mesorectal excision (TME) is still the go-to option, but it’s fraught with bad GI, urinary, sexual, and other complications for patients. “Consequently, the concept of organ preservation ... is very appealing,” Dr. Stitzenberg explained.

The chemoradiation/local excision approach she referenced is gaining traction as an alternative, but the radiation component is itself associated with substantial short- and long-term problems, including sphincter dysfunction and wound healing complications.

The goal of Dr. Kennecke’s study, dubbed NEO [Neoadjuvant, Excision, Observation], was to see if the radiation could be left out altogether.

Recruited at eight centers in Canada and one in the United States, the 58 subjects had clinical stage T1-T3 A/B node-negative tumors with no pathologic high-risk features.

They received neoadjuvant FOLFOX (six cycles in 32 patients, 91% completion rate) or CAPOX (four cycles in 26 patients, 89% completion); 56 of the 58 subjects then went on to transanal endoscopic tumor excision; one of the other two patients wasn’t eligible because of tumor progression and the other one declined.

The 33 patients who were stage T0/T1N0 after treatment were spared organ removal and underwent observation every 3-6 months. TME was recommended for the 23 others who were stage 2 or higher or had nodal metastases following chemotherapy and excision.

The numbers translated to a per-protocol organ preservation rate of 57% over a median follow-up of 15.4 months; when the 13 patients who declined TME were added, the rate climbed to 79%.

Although “organ preservation in rectal cancer is becoming an increasingly promising and realistic option for a subset of patients,” Dr. Stitzenberg said, there are more reasons to be cautious beyond the short follow-up.

“The standard of care treatment for these patients would have been proctectomy ... Most would not have [had] systemic chemotherapy. As a result, the added morbidity of FOLFOX or CAPOX needs to be considered.” The study reported that there were no unexpected toxicities, but “what were the expected toxicities? How many patients experienced grade 3 to 5 complications?” she wondered.

Also, how realistic is it to expect patients to report for surveillance every few months outside of a trial? And how can they best be watched to make sure recurrence is caught “while salvage TME is still feasible? There are many longer-term follow-up questions that remain to be answered,” Dr. Stitzenberg said.

Even with short follow-up, there were two locoregional recurrences across the cohort (3.5%), both treated by TME to R0/1 resection. There were no distant relapses.

Subjects were a median of 67 years old, and over two-thirds were men. The majority had stage 2 disease at baseline. Tumors were well to moderately differentiated nonmucinous rectal adenocarcinomas with a median height of 6 cm.

The work was funded by the Canadian Cancer Trials Group. Dr. Kennecke disclosed relationships with Advanced Accelerator Applications, Ipsen, and Taiho Pharmaceutical. Dr. Stitzenberg had no relevant disclosures.

aotto@mdedge.com

Medicare exacts a penalty whenever it deems that hospitals have too many patients with chronic obstructive pulmonary disease who have been re-admitted within 30 days of discharge for care related to the disease. For acute-care hospitals the solution to reducing chronic obstructive pulmonary disease (COPD) re-admissions has been elusive, but members of a COPD chronic care management collaborative think they have found at least a partial solution.

Among 33 centers participating in the performance improvement program, the aggregated cost avoidance for emergency department (ED) visits was estimated at $351,000, and the savings for hospital re-visits avoided was an estimated $2.6 million, reported Valerie Press, MD, MPH, from the University of Chicago, and co-authors from the health care performance-improvement company Vizient.

The investigators described their chronic care management collaborative in a thematic poster presented during the American Thoracic Society’s virtual international conference (Abstract A1688).

“I’ve been working in the space of COPD re-admissions pretty much since Medicare started its penalty program,” Dr. Press said in an interview.

“At both my own institution and nationally, we’ve been trying to understand the policy that went into place to reduce what was considered to be excessive readmissions after a COPD admission, but there really wasn’t a lot of evidence to suggest how to do this at the time the policy went into place,” she said.

The Centers for Medicare & Medicaid Services (CMS) initiated its Hospital Readmission Reduction Program for COPD in 2014.

“The challenge with COPD is that we have not found really successful interventions to decrease readmissions,” commented Laura C. Myers, MD, MPH, in an interview. Dr. Myers, who studies optimal care delivery models for patients with COPD at Kaiser Permanente Northern California in Oakland, was not involved in the study.

She said that although the aggregate cost savings in the study by Dr. Press and colleagues are relatively modest, “if you extrapolate across the country, then those numbers could potentially be impressive.”
 

Collaboration details

Dr. Press was a subject matter expert for the collaborative, which included 47 Vizient member sites in the Southeast, Southwest, Midwest, and Northeast and Northwest coasts. Of these centers, 33 completed both parts of the collaboration.

The program included bi-monthly didactic sessions and site report and discussion sessions with peer-to-peer networking for a total of 6 months. During the sessions, meeting participants discussed best practices, received expert coaching, and provided progress updates on performance improvement projects.

“The goal was for them to identify the gaps or needs they had at their hospitals or practices, and then to try to put in place one or more interventions,” Dr. Press said. “This wasn’t a research program. It wasn’t standardized, and not all hospitals had to do the same program.”

The participants submitted reports for baseline and post-collaboration periods on both an intervention’s “reach,” defined as the percentage of patients who received a specified intervention, and on two outcome measures.

The interventions measured included spirometry, follow-up visits scheduled within 7 to 14 days of discharge, patients receiving COPD education, pulmonary referrals, and adherence to the COPD clinical pathway.

The outcome measures were the rate of COPD-related ED visits and hospital readmissions.
 

Revisits reduced

At the end of the program, 83% of participating sites had reductions in either ED visits or readmissions, and of this group, five sites had decreases in both measures.

Among all sites with improved metrics, the average rate of COPD-related ED revisits declined from 12.7% to 9%, and average inpatient readmissions declined from 20.1% to 15.6%.

As noted, the estimated cost savings in ED revisits avoided was $351,00, and the estimated savings in hospital readmission costs was $2.6 million.

“Although the centers didn’t have to participate in both parts, we did see in our results that the programs that participated fully had better results,” Dr. Press said.

“Historically, we’ve had such difficulty in decreasing COPD readmissions, and it’s nice to see something that actually works, both for patients and for conserving health resources,” Dr. Myers commented.

The study was supported by Vizient. Dr. Press disclosed honoraria from the company in her role as subject matter expert. Dr. Myers reported no conflicts of interest.

Medicare exacts a penalty whenever it deems that hospitals have too many patients with chronic obstructive pulmonary disease who have been re-admitted within 30 days of discharge for care related to the disease. For acute-care hospitals the solution to reducing chronic obstructive pulmonary disease (COPD) re-admissions has been elusive, but members of a COPD chronic care management collaborative think they have found at least a partial solution.

Among 33 centers participating in the performance improvement program, the aggregated cost avoidance for emergency department (ED) visits was estimated at $351,000, and the savings for hospital re-visits avoided was an estimated $2.6 million, reported Valerie Press, MD, MPH, from the University of Chicago, and co-authors from the health care performance-improvement company Vizient.

The investigators described their chronic care management collaborative in a thematic poster presented during the American Thoracic Society’s virtual international conference (Abstract A1688).

“I’ve been working in the space of COPD re-admissions pretty much since Medicare started its penalty program,” Dr. Press said in an interview.

“At both my own institution and nationally, we’ve been trying to understand the policy that went into place to reduce what was considered to be excessive readmissions after a COPD admission, but there really wasn’t a lot of evidence to suggest how to do this at the time the policy went into place,” she said.

The Centers for Medicare & Medicaid Services (CMS) initiated its Hospital Readmission Reduction Program for COPD in 2014.

“The challenge with COPD is that we have not found really successful interventions to decrease readmissions,” commented Laura C. Myers, MD, MPH, in an interview. Dr. Myers, who studies optimal care delivery models for patients with COPD at Kaiser Permanente Northern California in Oakland, was not involved in the study.

She said that although the aggregate cost savings in the study by Dr. Press and colleagues are relatively modest, “if you extrapolate across the country, then those numbers could potentially be impressive.”
 

Collaboration details

Dr. Press was a subject matter expert for the collaborative, which included 47 Vizient member sites in the Southeast, Southwest, Midwest, and Northeast and Northwest coasts. Of these centers, 33 completed both parts of the collaboration.

The program included bi-monthly didactic sessions and site report and discussion sessions with peer-to-peer networking for a total of 6 months. During the sessions, meeting participants discussed best practices, received expert coaching, and provided progress updates on performance improvement projects.

“The goal was for them to identify the gaps or needs they had at their hospitals or practices, and then to try to put in place one or more interventions,” Dr. Press said. “This wasn’t a research program. It wasn’t standardized, and not all hospitals had to do the same program.”

The participants submitted reports for baseline and post-collaboration periods on both an intervention’s “reach,” defined as the percentage of patients who received a specified intervention, and on two outcome measures.

The interventions measured included spirometry, follow-up visits scheduled within 7 to 14 days of discharge, patients receiving COPD education, pulmonary referrals, and adherence to the COPD clinical pathway.

The outcome measures were the rate of COPD-related ED visits and hospital readmissions.
 

Revisits reduced

At the end of the program, 83% of participating sites had reductions in either ED visits or readmissions, and of this group, five sites had decreases in both measures.

Among all sites with improved metrics, the average rate of COPD-related ED revisits declined from 12.7% to 9%, and average inpatient readmissions declined from 20.1% to 15.6%.

As noted, the estimated cost savings in ED revisits avoided was $351,00, and the estimated savings in hospital readmission costs was $2.6 million.

“Although the centers didn’t have to participate in both parts, we did see in our results that the programs that participated fully had better results,” Dr. Press said.

“Historically, we’ve had such difficulty in decreasing COPD readmissions, and it’s nice to see something that actually works, both for patients and for conserving health resources,” Dr. Myers commented.

The study was supported by Vizient. Dr. Press disclosed honoraria from the company in her role as subject matter expert. Dr. Myers reported no conflicts of interest.

Medicare exacts a penalty whenever it deems that hospitals have too many patients with chronic obstructive pulmonary disease who have been re-admitted within 30 days of discharge for care related to the disease. For acute-care hospitals the solution to reducing chronic obstructive pulmonary disease (COPD) re-admissions has been elusive, but members of a COPD chronic care management collaborative think they have found at least a partial solution.

Among 33 centers participating in the performance improvement program, the aggregated cost avoidance for emergency department (ED) visits was estimated at $351,000, and the savings for hospital re-visits avoided was an estimated $2.6 million, reported Valerie Press, MD, MPH, from the University of Chicago, and co-authors from the health care performance-improvement company Vizient.

The investigators described their chronic care management collaborative in a thematic poster presented during the American Thoracic Society’s virtual international conference (Abstract A1688).

“I’ve been working in the space of COPD re-admissions pretty much since Medicare started its penalty program,” Dr. Press said in an interview.

“At both my own institution and nationally, we’ve been trying to understand the policy that went into place to reduce what was considered to be excessive readmissions after a COPD admission, but there really wasn’t a lot of evidence to suggest how to do this at the time the policy went into place,” she said.

The Centers for Medicare & Medicaid Services (CMS) initiated its Hospital Readmission Reduction Program for COPD in 2014.

“The challenge with COPD is that we have not found really successful interventions to decrease readmissions,” commented Laura C. Myers, MD, MPH, in an interview. Dr. Myers, who studies optimal care delivery models for patients with COPD at Kaiser Permanente Northern California in Oakland, was not involved in the study.

She said that although the aggregate cost savings in the study by Dr. Press and colleagues are relatively modest, “if you extrapolate across the country, then those numbers could potentially be impressive.”
 

Collaboration details

Dr. Press was a subject matter expert for the collaborative, which included 47 Vizient member sites in the Southeast, Southwest, Midwest, and Northeast and Northwest coasts. Of these centers, 33 completed both parts of the collaboration.

The program included bi-monthly didactic sessions and site report and discussion sessions with peer-to-peer networking for a total of 6 months. During the sessions, meeting participants discussed best practices, received expert coaching, and provided progress updates on performance improvement projects.

“The goal was for them to identify the gaps or needs they had at their hospitals or practices, and then to try to put in place one or more interventions,” Dr. Press said. “This wasn’t a research program. It wasn’t standardized, and not all hospitals had to do the same program.”

The participants submitted reports for baseline and post-collaboration periods on both an intervention’s “reach,” defined as the percentage of patients who received a specified intervention, and on two outcome measures.

The interventions measured included spirometry, follow-up visits scheduled within 7 to 14 days of discharge, patients receiving COPD education, pulmonary referrals, and adherence to the COPD clinical pathway.

The outcome measures were the rate of COPD-related ED visits and hospital readmissions.
 

Revisits reduced

At the end of the program, 83% of participating sites had reductions in either ED visits or readmissions, and of this group, five sites had decreases in both measures.

Among all sites with improved metrics, the average rate of COPD-related ED revisits declined from 12.7% to 9%, and average inpatient readmissions declined from 20.1% to 15.6%.

As noted, the estimated cost savings in ED revisits avoided was $351,00, and the estimated savings in hospital readmission costs was $2.6 million.

“Although the centers didn’t have to participate in both parts, we did see in our results that the programs that participated fully had better results,” Dr. Press said.

“Historically, we’ve had such difficulty in decreasing COPD readmissions, and it’s nice to see something that actually works, both for patients and for conserving health resources,” Dr. Myers commented.

The study was supported by Vizient. Dr. Press disclosed honoraria from the company in her role as subject matter expert. Dr. Myers reported no conflicts of interest.

The first KRAS inhibitor approved for the treatment of lung cancer provided a clinically meaningful overall survival benefit in an updated analysis of a phase 2 study.

Treatment with sotorasib yielded a median overall survival (OS) of 12.5 months in patients with previously treated KRAS p.G12C-mutated non-small cell lung cancer (NSCLC), according to an analysis of the phase 2 CodeBreaK 100 trial data presented at the American Society of Clinical Oncology Annual Meeting.

Median progression-free survival (PFS) was 6.8 months in this update, which included a median follow-up of more than 15 months, according to investigator Ferdinandos Skoulidis, MD, PhD, assistant professor of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

Efficacy responses

The confirmed objective response rate was 37.1%, including a 3.2% complete response rate and a median duration of response of 11.1 months, according to the report by Dr. Skoulidis.

In exploratory analyses, the benefit of sotorasib was consistent across patient subgroups, Dr. Skoulidis said in his presentation (Abstract 9003).

In particular, efficacy was observed in subgroups with co-occurring mutations in TP53, STK11, and KEAP1, which are molecular indicators of suboptimal outcomes on standard systemic treatments, according to Dr. Skoulidis.

This update on the registrational phase 2 CodeBreaK100 trial, published concurrently in the New England Journal of Medicine , came just one week after the U.S. Food and Drug Administration (FDA) granted accelerated approval to sotorasib.

Sotorasib was approved for the treatment of patients with previously treated KRAS G12C‑mutated locally advanced or metastatic NSCLC on the basis of previously reported results from CodeBreaK100.

This sotorasib indication represents a “historic milestone,” Dr. Skoulidis said in an interview.

No previously studied selective KRAS inhibitor has been approved despite scientific research efforts that stretch back nearly four decades, he explained.

“In a way, one can say that we have dealt KRAS-mutant lung cancer a knockdown blow, however, I should point out that the fight is not over,” he added.

“These clinical results will no doubt spearhead and galvanize further efforts to develop even more effective therapeutic combinations in the future, as well as identify and either forestall or overcome the eventual development of acquired resistance,” he said.
 

Only 1 out of 8 patients

The KRAS p.G12C mutation is present in about 13% of lung adenocarcinomas, or about one in every eight patients with nonsquamous NSCLC, Dr. Skoulidis said in the interview.

“We are estimating that this is in the region of 13,000 patients newly diagnosed every year in the U.S., and approximately 13,000 patients or so that are currently being treated in the second- or third-line setting,” he said.

The CodeBreaK100 trial included 126 patients with locally advanced or metastatic NSCLC and KRAS p.G12C mutation who had progressed on prior systemic therapies. About 43% had one prior line of treatment, while 35% had two lines, and 22% had three lines. A total of 81% had previously received both platinum-based chemotherapy and PD-1/PD-L1 axis inhibitors.

Most treatment-related adverse events in the study were grade 1-2 and generally manageable, according to Dr. Skoulidis. About 20% of patients experienced grade 3 treatment-related adverse events, which were mostly diarrhea or increases in aspartate aminotransferase and alanine aminotransferase levels. A grade 4 treatment-related adverse event, pneumonitis and dyspnea, was reported in one patient or approximately 1%.
 

Confirmatory trial

Although CodeBreak100 is not a randomized trial, the median OS of 12.5 months compares favorably to median OS times in the range of 7.9-10.3 months reported in randomized phase 3 clinical trials and subgroup analysis of randomized phase 3 trials of docetaxel for patients with KRAS-mutant lung adenocarcinoma, Dr. Skoulidis said in a question-and-answer session.

A confirmatory phase 3 CodeBreaK200 trial of sotorasib versus docetaxel in patients with previously treated KRAS p.G12C-mutated NSCLC is underway. That trial is evaluating PFS as a primary endpoint and OS as a secondary endpoint.

“If the same magnitude of benefit, 12.5 months median overall survival, is confirmed in the larger phase 3 clinical trial, as a clinician I would consider that beneficial for patients, compared to the standard of care,” Dr. Skoulidis said during the session.
 

Mature data

The updated analysis of the phase 2 CodeBreaK100 study is notable for its mature OS data, updated safety and the first molecular subgroup analyses, according to discussant Christine Marie Lovly, MD, PhD, of the division of hematology-oncology at Vanderbilt University Medical Center in Nashville.

“The objective response rate was 37.1%,” she added. “This is a little bit lower than we’re used to for targeted therapies, but remember, this is a different mutation and a very different class of drugs.”

The KRAS G12C inhibitors, several of which are under clinical development, are not tyrosine kinase inhibitors (TKIs), but rather allele-specific inhibitors that target mutant KRAS, trapping it in an inactive conformation, she explained.

Dr. Lovly referenced the exploratory analyses demonstrating efficacy in molecularly defined subgroups, calling it “interesting” that there was no difference in objective response rate between TP53 wild type and mutant tumors.

“We do have data that mutant TP53 seems to confer inferior outcomes for EGFR TKI-directed therapy in patients with EGFR-mutant lung cancer,” she said.

CodeBreaK100 was supported by Amgen, Inc. and partly by a National Institutes of Health Cancer Center Support Grant at Memorial Sloan Kettering Cancer Center.

Dr. Skoulidis reported honoraria from Bristol-Myers Squibb; research funding from AIMM Therapeutics and Amgen; and travel, accommodations, or expenses from Tango Therapeutics. Dr. Lovly reported disclosures related to Amgen, AstraZeneca, Genentech, Novartis, and Pfizer, among others.

The first KRAS inhibitor approved for the treatment of lung cancer provided a clinically meaningful overall survival benefit in an updated analysis of a phase 2 study.

Treatment with sotorasib yielded a median overall survival (OS) of 12.5 months in patients with previously treated KRAS p.G12C-mutated non-small cell lung cancer (NSCLC), according to an analysis of the phase 2 CodeBreaK 100 trial data presented at the American Society of Clinical Oncology Annual Meeting.

Median progression-free survival (PFS) was 6.8 months in this update, which included a median follow-up of more than 15 months, according to investigator Ferdinandos Skoulidis, MD, PhD, assistant professor of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

Efficacy responses

The confirmed objective response rate was 37.1%, including a 3.2% complete response rate and a median duration of response of 11.1 months, according to the report by Dr. Skoulidis.

In exploratory analyses, the benefit of sotorasib was consistent across patient subgroups, Dr. Skoulidis said in his presentation (Abstract 9003).

In particular, efficacy was observed in subgroups with co-occurring mutations in TP53, STK11, and KEAP1, which are molecular indicators of suboptimal outcomes on standard systemic treatments, according to Dr. Skoulidis.

This update on the registrational phase 2 CodeBreaK100 trial, published concurrently in the New England Journal of Medicine , came just one week after the U.S. Food and Drug Administration (FDA) granted accelerated approval to sotorasib.

Sotorasib was approved for the treatment of patients with previously treated KRAS G12C‑mutated locally advanced or metastatic NSCLC on the basis of previously reported results from CodeBreaK100.

This sotorasib indication represents a “historic milestone,” Dr. Skoulidis said in an interview.

No previously studied selective KRAS inhibitor has been approved despite scientific research efforts that stretch back nearly four decades, he explained.

“In a way, one can say that we have dealt KRAS-mutant lung cancer a knockdown blow, however, I should point out that the fight is not over,” he added.

“These clinical results will no doubt spearhead and galvanize further efforts to develop even more effective therapeutic combinations in the future, as well as identify and either forestall or overcome the eventual development of acquired resistance,” he said.
 

Only 1 out of 8 patients

The KRAS p.G12C mutation is present in about 13% of lung adenocarcinomas, or about one in every eight patients with nonsquamous NSCLC, Dr. Skoulidis said in the interview.

“We are estimating that this is in the region of 13,000 patients newly diagnosed every year in the U.S., and approximately 13,000 patients or so that are currently being treated in the second- or third-line setting,” he said.

The CodeBreaK100 trial included 126 patients with locally advanced or metastatic NSCLC and KRAS p.G12C mutation who had progressed on prior systemic therapies. About 43% had one prior line of treatment, while 35% had two lines, and 22% had three lines. A total of 81% had previously received both platinum-based chemotherapy and PD-1/PD-L1 axis inhibitors.

Most treatment-related adverse events in the study were grade 1-2 and generally manageable, according to Dr. Skoulidis. About 20% of patients experienced grade 3 treatment-related adverse events, which were mostly diarrhea or increases in aspartate aminotransferase and alanine aminotransferase levels. A grade 4 treatment-related adverse event, pneumonitis and dyspnea, was reported in one patient or approximately 1%.
 

Confirmatory trial

Although CodeBreak100 is not a randomized trial, the median OS of 12.5 months compares favorably to median OS times in the range of 7.9-10.3 months reported in randomized phase 3 clinical trials and subgroup analysis of randomized phase 3 trials of docetaxel for patients with KRAS-mutant lung adenocarcinoma, Dr. Skoulidis said in a question-and-answer session.

A confirmatory phase 3 CodeBreaK200 trial of sotorasib versus docetaxel in patients with previously treated KRAS p.G12C-mutated NSCLC is underway. That trial is evaluating PFS as a primary endpoint and OS as a secondary endpoint.

“If the same magnitude of benefit, 12.5 months median overall survival, is confirmed in the larger phase 3 clinical trial, as a clinician I would consider that beneficial for patients, compared to the standard of care,” Dr. Skoulidis said during the session.
 

Mature data

The updated analysis of the phase 2 CodeBreaK100 study is notable for its mature OS data, updated safety and the first molecular subgroup analyses, according to discussant Christine Marie Lovly, MD, PhD, of the division of hematology-oncology at Vanderbilt University Medical Center in Nashville.

“The objective response rate was 37.1%,” she added. “This is a little bit lower than we’re used to for targeted therapies, but remember, this is a different mutation and a very different class of drugs.”

The KRAS G12C inhibitors, several of which are under clinical development, are not tyrosine kinase inhibitors (TKIs), but rather allele-specific inhibitors that target mutant KRAS, trapping it in an inactive conformation, she explained.

Dr. Lovly referenced the exploratory analyses demonstrating efficacy in molecularly defined subgroups, calling it “interesting” that there was no difference in objective response rate between TP53 wild type and mutant tumors.

“We do have data that mutant TP53 seems to confer inferior outcomes for EGFR TKI-directed therapy in patients with EGFR-mutant lung cancer,” she said.

CodeBreaK100 was supported by Amgen, Inc. and partly by a National Institutes of Health Cancer Center Support Grant at Memorial Sloan Kettering Cancer Center.

Dr. Skoulidis reported honoraria from Bristol-Myers Squibb; research funding from AIMM Therapeutics and Amgen; and travel, accommodations, or expenses from Tango Therapeutics. Dr. Lovly reported disclosures related to Amgen, AstraZeneca, Genentech, Novartis, and Pfizer, among others.

The first KRAS inhibitor approved for the treatment of lung cancer provided a clinically meaningful overall survival benefit in an updated analysis of a phase 2 study.

Treatment with sotorasib yielded a median overall survival (OS) of 12.5 months in patients with previously treated KRAS p.G12C-mutated non-small cell lung cancer (NSCLC), according to an analysis of the phase 2 CodeBreaK 100 trial data presented at the American Society of Clinical Oncology Annual Meeting.

Median progression-free survival (PFS) was 6.8 months in this update, which included a median follow-up of more than 15 months, according to investigator Ferdinandos Skoulidis, MD, PhD, assistant professor of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

Efficacy responses

The confirmed objective response rate was 37.1%, including a 3.2% complete response rate and a median duration of response of 11.1 months, according to the report by Dr. Skoulidis.

In exploratory analyses, the benefit of sotorasib was consistent across patient subgroups, Dr. Skoulidis said in his presentation (Abstract 9003).

In particular, efficacy was observed in subgroups with co-occurring mutations in TP53, STK11, and KEAP1, which are molecular indicators of suboptimal outcomes on standard systemic treatments, according to Dr. Skoulidis.

This update on the registrational phase 2 CodeBreaK100 trial, published concurrently in the New England Journal of Medicine , came just one week after the U.S. Food and Drug Administration (FDA) granted accelerated approval to sotorasib.

Sotorasib was approved for the treatment of patients with previously treated KRAS G12C‑mutated locally advanced or metastatic NSCLC on the basis of previously reported results from CodeBreaK100.

This sotorasib indication represents a “historic milestone,” Dr. Skoulidis said in an interview.

No previously studied selective KRAS inhibitor has been approved despite scientific research efforts that stretch back nearly four decades, he explained.

“In a way, one can say that we have dealt KRAS-mutant lung cancer a knockdown blow, however, I should point out that the fight is not over,” he added.

“These clinical results will no doubt spearhead and galvanize further efforts to develop even more effective therapeutic combinations in the future, as well as identify and either forestall or overcome the eventual development of acquired resistance,” he said.
 

Only 1 out of 8 patients

The KRAS p.G12C mutation is present in about 13% of lung adenocarcinomas, or about one in every eight patients with nonsquamous NSCLC, Dr. Skoulidis said in the interview.

“We are estimating that this is in the region of 13,000 patients newly diagnosed every year in the U.S., and approximately 13,000 patients or so that are currently being treated in the second- or third-line setting,” he said.

The CodeBreaK100 trial included 126 patients with locally advanced or metastatic NSCLC and KRAS p.G12C mutation who had progressed on prior systemic therapies. About 43% had one prior line of treatment, while 35% had two lines, and 22% had three lines. A total of 81% had previously received both platinum-based chemotherapy and PD-1/PD-L1 axis inhibitors.

Most treatment-related adverse events in the study were grade 1-2 and generally manageable, according to Dr. Skoulidis. About 20% of patients experienced grade 3 treatment-related adverse events, which were mostly diarrhea or increases in aspartate aminotransferase and alanine aminotransferase levels. A grade 4 treatment-related adverse event, pneumonitis and dyspnea, was reported in one patient or approximately 1%.
 

Confirmatory trial

Although CodeBreak100 is not a randomized trial, the median OS of 12.5 months compares favorably to median OS times in the range of 7.9-10.3 months reported in randomized phase 3 clinical trials and subgroup analysis of randomized phase 3 trials of docetaxel for patients with KRAS-mutant lung adenocarcinoma, Dr. Skoulidis said in a question-and-answer session.

A confirmatory phase 3 CodeBreaK200 trial of sotorasib versus docetaxel in patients with previously treated KRAS p.G12C-mutated NSCLC is underway. That trial is evaluating PFS as a primary endpoint and OS as a secondary endpoint.

“If the same magnitude of benefit, 12.5 months median overall survival, is confirmed in the larger phase 3 clinical trial, as a clinician I would consider that beneficial for patients, compared to the standard of care,” Dr. Skoulidis said during the session.
 

Mature data

The updated analysis of the phase 2 CodeBreaK100 study is notable for its mature OS data, updated safety and the first molecular subgroup analyses, according to discussant Christine Marie Lovly, MD, PhD, of the division of hematology-oncology at Vanderbilt University Medical Center in Nashville.

“The objective response rate was 37.1%,” she added. “This is a little bit lower than we’re used to for targeted therapies, but remember, this is a different mutation and a very different class of drugs.”

The KRAS G12C inhibitors, several of which are under clinical development, are not tyrosine kinase inhibitors (TKIs), but rather allele-specific inhibitors that target mutant KRAS, trapping it in an inactive conformation, she explained.

Dr. Lovly referenced the exploratory analyses demonstrating efficacy in molecularly defined subgroups, calling it “interesting” that there was no difference in objective response rate between TP53 wild type and mutant tumors.

“We do have data that mutant TP53 seems to confer inferior outcomes for EGFR TKI-directed therapy in patients with EGFR-mutant lung cancer,” she said.

CodeBreaK100 was supported by Amgen, Inc. and partly by a National Institutes of Health Cancer Center Support Grant at Memorial Sloan Kettering Cancer Center.

Dr. Skoulidis reported honoraria from Bristol-Myers Squibb; research funding from AIMM Therapeutics and Amgen; and travel, accommodations, or expenses from Tango Therapeutics. Dr. Lovly reported disclosures related to Amgen, AstraZeneca, Genentech, Novartis, and Pfizer, among others.

Lung cancer patients treated in community practices are not being comprehensively tested for biomarkers that could guide choice of first-line therapy, a recent retrospective analysis shows.

Less than half of patients with previously untreated non-small cell lung cancer (NSCLC) in a network of community practices underwent testing for all five biomarkers evaluated in the study, which was presented at the annual meeting of the American Society of Clinical Oncology (Abstract 9004).

Almost all of the 3,474 patients in the study (90%) had been tested for at least one biomarker, according to investigator Makenzi Colleen Evangelist, MD, an oncologist with New York Oncology Hematology, a practice in the US Oncology Network.

Only 46% were tested for all five biomarkers—ALK, BRAF, EGFR, ROS1, and PD-L1.

“While the proportion of patients tested for all five biomarkers increased over time, testing rates remain low at approximately 50%,” Dr. Evangelist said in a presentation of the results at the meeting.

This gap in testing illustrates “significant implementation challenges” that exist despite tremendous advances in biomarker-driven drug development and the technology to detect the mutations that can guide therapy, said Christine Marie Lovly, MD, PhD, the invited discussant for the study. “I would strongly argue that we have to apply what we already have to get equity, while still pushing the science forward,” said Dr. Lovly of the division of hematology-oncology at Vanderbilt University Medical Center in Nashville.

“We don’t want to miss the low-hanging fruit,” Dr. Lovly said. “We have to be able to make sure every patient with an EGFR mutation gets an EGFR tyrosine kinase inhibitor, and so forth, for all the other biomarkers that we test for.”
 

Real-world testing

The retrospective analysis of real-world biomarker testing patterns presented by Dr. Evangelist is the first of three protocols in the MYLUNG Consortium, a collaborative research study being conducted over a five-year period, according to the US Oncology Network.

The review of electronic health records included patients with metastatic NSCLC starting first-line systemic therapy between April 2018 and March 2020 in the US Oncology Network of community practices.

Rates of biomarker testing were highest for PD-L1, which was done for 83% of patients, the data show. EGFR and ALK testing were performed in 70% of patients, while ROS1 was evaluated in 68%. BRAF testing was done in 55% of patients. Testing rates appeared to be numerically higher for lung cancers with nonsquamous histology, according to Dr. Evangelist.

Over time, rates of specific biomarker testing were essentially unchanged, though a significant difference was seen for BRAF testing over time. BRAF was evaluated in 54% of patients starting therapy from April 2018 through September 2018, and 59%-62% in subsequent time periods (P = .005).

The proportion of patients tested for all five biomarkers was 44% in the April-September 2018 time period, and 50%-53% in subsequent time periods, the data show (P = .0056).

The proportion of patients tested with next-generation sequencing rose from 33% to 45% between 2018 and 2020, suggesting that comprehensive testing is increasing, according to Dr. Evangelist.

The turnaround time from testing orders to results was approximately 2 weeks, underscoring a need to get test results to oncologists sooner so they can consider biomarker data as they develop a treatment plan, the US Oncology Network said in a press release that described the study.

Median time from diagnosis to treatment in the study was approximately 5 weeks, which is “a concern for patients anxiously waiting for treatment,” the press release said.
 

Raising awareness

This study should serve to raise awareness that not all NSCLC patients who should be tested are being tested, study co-author Nicholas Robert, MD, said in an interview.

“There is a great line – ‘right drug, right patient, right time’ – and we’re not meeting that,” said Dr. Robert, vice president of medical affairs for Ontada, an oncology insights and technology company that is part of McKesson, which acquired the US Oncology Network in 2010.

The hope is that general oncologists will begin thinking of biomarker testing in NSCLC as being essential in the same way hormone receptor and HER2 testing are in breast cancer, according to Dr. Robert.

“You would never think about treating anyone with breast cancer without those variables,” he said. “We’d like to think that the general oncologist feels the same way about biomarkers in non-small cell cancer, that it’s something that should be done routinely across the board.”

The next phase of the MYLUNG Consortium study will prospectively evaluate biomarker test-ordering practices, turnaround times, and treatment decision making in approximately 1,000 patients from 11 sites, while the final phase will evaluate interventions to improve biomarker testing and access to therapies in up to 7,500 patients at 20 sites, according to the US Oncology Network.

Dr. Evangelist reported a consulting or advisory role with Takeda and AstraZeneca. Dr. Robert reported employment, leadership, and stock/ownership interest disclosures related to McKesson, along with other disclosures related to Johnson & Johnson, Oncolytics Biotech, Bristol-Myers Squibb, Roche, Advi, Boehringer Ingelheim, and New Century Health. Dr. Lovly reported disclosures related to Amgen, AstraZeneca, Genentech, Novartis, and Pfizer, among others.

Lung cancer patients treated in community practices are not being comprehensively tested for biomarkers that could guide choice of first-line therapy, a recent retrospective analysis shows.

Less than half of patients with previously untreated non-small cell lung cancer (NSCLC) in a network of community practices underwent testing for all five biomarkers evaluated in the study, which was presented at the annual meeting of the American Society of Clinical Oncology (Abstract 9004).

Almost all of the 3,474 patients in the study (90%) had been tested for at least one biomarker, according to investigator Makenzi Colleen Evangelist, MD, an oncologist with New York Oncology Hematology, a practice in the US Oncology Network.

Only 46% were tested for all five biomarkers—ALK, BRAF, EGFR, ROS1, and PD-L1.

“While the proportion of patients tested for all five biomarkers increased over time, testing rates remain low at approximately 50%,” Dr. Evangelist said in a presentation of the results at the meeting.

This gap in testing illustrates “significant implementation challenges” that exist despite tremendous advances in biomarker-driven drug development and the technology to detect the mutations that can guide therapy, said Christine Marie Lovly, MD, PhD, the invited discussant for the study. “I would strongly argue that we have to apply what we already have to get equity, while still pushing the science forward,” said Dr. Lovly of the division of hematology-oncology at Vanderbilt University Medical Center in Nashville.

“We don’t want to miss the low-hanging fruit,” Dr. Lovly said. “We have to be able to make sure every patient with an EGFR mutation gets an EGFR tyrosine kinase inhibitor, and so forth, for all the other biomarkers that we test for.”
 

Real-world testing

The retrospective analysis of real-world biomarker testing patterns presented by Dr. Evangelist is the first of three protocols in the MYLUNG Consortium, a collaborative research study being conducted over a five-year period, according to the US Oncology Network.

The review of electronic health records included patients with metastatic NSCLC starting first-line systemic therapy between April 2018 and March 2020 in the US Oncology Network of community practices.

Rates of biomarker testing were highest for PD-L1, which was done for 83% of patients, the data show. EGFR and ALK testing were performed in 70% of patients, while ROS1 was evaluated in 68%. BRAF testing was done in 55% of patients. Testing rates appeared to be numerically higher for lung cancers with nonsquamous histology, according to Dr. Evangelist.

Over time, rates of specific biomarker testing were essentially unchanged, though a significant difference was seen for BRAF testing over time. BRAF was evaluated in 54% of patients starting therapy from April 2018 through September 2018, and 59%-62% in subsequent time periods (P = .005).

The proportion of patients tested for all five biomarkers was 44% in the April-September 2018 time period, and 50%-53% in subsequent time periods, the data show (P = .0056).

The proportion of patients tested with next-generation sequencing rose from 33% to 45% between 2018 and 2020, suggesting that comprehensive testing is increasing, according to Dr. Evangelist.

The turnaround time from testing orders to results was approximately 2 weeks, underscoring a need to get test results to oncologists sooner so they can consider biomarker data as they develop a treatment plan, the US Oncology Network said in a press release that described the study.

Median time from diagnosis to treatment in the study was approximately 5 weeks, which is “a concern for patients anxiously waiting for treatment,” the press release said.
 

Raising awareness

This study should serve to raise awareness that not all NSCLC patients who should be tested are being tested, study co-author Nicholas Robert, MD, said in an interview.

“There is a great line – ‘right drug, right patient, right time’ – and we’re not meeting that,” said Dr. Robert, vice president of medical affairs for Ontada, an oncology insights and technology company that is part of McKesson, which acquired the US Oncology Network in 2010.

The hope is that general oncologists will begin thinking of biomarker testing in NSCLC as being essential in the same way hormone receptor and HER2 testing are in breast cancer, according to Dr. Robert.

“You would never think about treating anyone with breast cancer without those variables,” he said. “We’d like to think that the general oncologist feels the same way about biomarkers in non-small cell cancer, that it’s something that should be done routinely across the board.”

The next phase of the MYLUNG Consortium study will prospectively evaluate biomarker test-ordering practices, turnaround times, and treatment decision making in approximately 1,000 patients from 11 sites, while the final phase will evaluate interventions to improve biomarker testing and access to therapies in up to 7,500 patients at 20 sites, according to the US Oncology Network.

Dr. Evangelist reported a consulting or advisory role with Takeda and AstraZeneca. Dr. Robert reported employment, leadership, and stock/ownership interest disclosures related to McKesson, along with other disclosures related to Johnson & Johnson, Oncolytics Biotech, Bristol-Myers Squibb, Roche, Advi, Boehringer Ingelheim, and New Century Health. Dr. Lovly reported disclosures related to Amgen, AstraZeneca, Genentech, Novartis, and Pfizer, among others.

Lung cancer patients treated in community practices are not being comprehensively tested for biomarkers that could guide choice of first-line therapy, a recent retrospective analysis shows.

Less than half of patients with previously untreated non-small cell lung cancer (NSCLC) in a network of community practices underwent testing for all five biomarkers evaluated in the study, which was presented at the annual meeting of the American Society of Clinical Oncology (Abstract 9004).

Almost all of the 3,474 patients in the study (90%) had been tested for at least one biomarker, according to investigator Makenzi Colleen Evangelist, MD, an oncologist with New York Oncology Hematology, a practice in the US Oncology Network.

Only 46% were tested for all five biomarkers—ALK, BRAF, EGFR, ROS1, and PD-L1.

“While the proportion of patients tested for all five biomarkers increased over time, testing rates remain low at approximately 50%,” Dr. Evangelist said in a presentation of the results at the meeting.

This gap in testing illustrates “significant implementation challenges” that exist despite tremendous advances in biomarker-driven drug development and the technology to detect the mutations that can guide therapy, said Christine Marie Lovly, MD, PhD, the invited discussant for the study. “I would strongly argue that we have to apply what we already have to get equity, while still pushing the science forward,” said Dr. Lovly of the division of hematology-oncology at Vanderbilt University Medical Center in Nashville.

“We don’t want to miss the low-hanging fruit,” Dr. Lovly said. “We have to be able to make sure every patient with an EGFR mutation gets an EGFR tyrosine kinase inhibitor, and so forth, for all the other biomarkers that we test for.”
 

Real-world testing

The retrospective analysis of real-world biomarker testing patterns presented by Dr. Evangelist is the first of three protocols in the MYLUNG Consortium, a collaborative research study being conducted over a five-year period, according to the US Oncology Network.

The review of electronic health records included patients with metastatic NSCLC starting first-line systemic therapy between April 2018 and March 2020 in the US Oncology Network of community practices.

Rates of biomarker testing were highest for PD-L1, which was done for 83% of patients, the data show. EGFR and ALK testing were performed in 70% of patients, while ROS1 was evaluated in 68%. BRAF testing was done in 55% of patients. Testing rates appeared to be numerically higher for lung cancers with nonsquamous histology, according to Dr. Evangelist.

Over time, rates of specific biomarker testing were essentially unchanged, though a significant difference was seen for BRAF testing over time. BRAF was evaluated in 54% of patients starting therapy from April 2018 through September 2018, and 59%-62% in subsequent time periods (P = .005).

The proportion of patients tested for all five biomarkers was 44% in the April-September 2018 time period, and 50%-53% in subsequent time periods, the data show (P = .0056).

The proportion of patients tested with next-generation sequencing rose from 33% to 45% between 2018 and 2020, suggesting that comprehensive testing is increasing, according to Dr. Evangelist.

The turnaround time from testing orders to results was approximately 2 weeks, underscoring a need to get test results to oncologists sooner so they can consider biomarker data as they develop a treatment plan, the US Oncology Network said in a press release that described the study.

Median time from diagnosis to treatment in the study was approximately 5 weeks, which is “a concern for patients anxiously waiting for treatment,” the press release said.
 

Raising awareness

This study should serve to raise awareness that not all NSCLC patients who should be tested are being tested, study co-author Nicholas Robert, MD, said in an interview.

“There is a great line – ‘right drug, right patient, right time’ – and we’re not meeting that,” said Dr. Robert, vice president of medical affairs for Ontada, an oncology insights and technology company that is part of McKesson, which acquired the US Oncology Network in 2010.

The hope is that general oncologists will begin thinking of biomarker testing in NSCLC as being essential in the same way hormone receptor and HER2 testing are in breast cancer, according to Dr. Robert.

“You would never think about treating anyone with breast cancer without those variables,” he said. “We’d like to think that the general oncologist feels the same way about biomarkers in non-small cell cancer, that it’s something that should be done routinely across the board.”

The next phase of the MYLUNG Consortium study will prospectively evaluate biomarker test-ordering practices, turnaround times, and treatment decision making in approximately 1,000 patients from 11 sites, while the final phase will evaluate interventions to improve biomarker testing and access to therapies in up to 7,500 patients at 20 sites, according to the US Oncology Network.

Dr. Evangelist reported a consulting or advisory role with Takeda and AstraZeneca. Dr. Robert reported employment, leadership, and stock/ownership interest disclosures related to McKesson, along with other disclosures related to Johnson & Johnson, Oncolytics Biotech, Bristol-Myers Squibb, Roche, Advi, Boehringer Ingelheim, and New Century Health. Dr. Lovly reported disclosures related to Amgen, AstraZeneca, Genentech, Novartis, and Pfizer, among others.

Experiencing an immune-related adverse event during checkpoint inhibitor treatment may predict outcomes in patients with non-small cell lung cancer, exploratory analyses of phase 3 trials suggest.

Immune-related adverse events (irAEs) were tied to longer overall survival (OS) in exploratory pooled analyses of three phase 3 clinical trials evaluating atezolizumab-based regimens, according to investigator Mark A. Socinski, MD, of AdventHealth Cancer Institute, Orlando, Fla.

Median OS approached 26 months for patients who received first-line atezolizumab and experienced an irAE, compared with just 13 months for those who did not experience an irAE, according to results reported at the American Society of Clinical Oncology Annual Meeting (Abstract 9002).

Atezolizumab-treated patients with grade 3 or greater irAEs had the shortest OS, shorter than those atezolizumab-treated patients who experienced grade 1-2 irAEs or no irAEs at all. That short OS may be due to treatment interruptions or discontinuations, said Dr. Socinski.

“Data from these analyses suggest an association between irAEs and efficacy in patients with [non-small cell cancer] NSCLC,” he stated in his presentation of the results.
 

A lot more to learn about irAEs

Similar linkages between irAEs and outcomes were observed in pooled analyses of patients enrolled in the control arms of the phase 3 trials, with a median OS of about 20 months for control patients experiencing an irAE, versus about 13 months for those who did not.

That linkage in the control arm prompted a question from an ASCO attendee about why an effect of irAEs, commonly associated with immune checkpoint inhibitor therapy, would be evident in analyses of patients who did not receive those agents.

In his response, Dr. Socinski characterized the finding as “a surprise” and said the finding may either reflect how adverse events are characterized or how chemotherapy impacts the immune system.

“I don’t know that our definition of irAEs is perfect,” he said, “and maybe we don’t understand what impact chemotherapy may have on the immune system, and may actually engender what historically we’ve always seen as an adverse event, but didn’t necessarily classify as an immune-related adverse event.”

More work is needed to better understand the connection between irAES and outcomes, and whether anything can be done as a result of that improved understanding, said discussant Mary Weber Redman, PhD.

“The question is, ‘what is actionable?’” added Dr. Redman, a biostatistician at the Fred Hutchinson Cancer Research Center, Seattle.

A firmer understanding of the relationship between irAEs and outcomes could change how clinicians monitor patients for irAEs, lead to better prediction of which patients may experience higher grade irAEs, and ultimately impact treatment selection potentially to avoid those higher grade events, Dr. Redman said in her remarks.

“Doing these types of analyses are quite important, because we have to look at the breadth of information that we have to be able to interpret that and think about what are future questions,” she said in the question-and-answer session accompanying Dr. Socinski’s presentation.

“I think the key is that we shouldn’t use these analyses to be definitive, but we should use them as to be hypothesis generating,” she added.
 

More evidence to link irAEs and outcomes

Immune-related AEs caused by off-target immune and inflammatory activity have been reported in up to 80% of patients receiving immune checkpoint inhibitors as monotherapy and up to 95% in combination regimens, Dr. Socinski said in his presentation.

“Increasing evidence suggests that the occurrence of immune-related adverse events with PD-L1 or PD-1 inhibitor therapy may be predictive of improved outcomes in cancers such as NSCLC, “ he added.

In their exploratory pooled analyses, Dr. Socinski and co-investigators looked at data from the phase 3 IMpower130 and IMpower132 trials, which evaluated first-line atezolizumab and chemotherapy for NSCLC, and the phase 3 IMpower150 trial, which evaluated atezolizumab plus chemotherapy with or without bevacizumab.

In all, they analyzed data for 1,557 atezolizumab-treated patients, and 900 patients who had been in the control arms of the studies.

Forty-eight percent of atezolizumab-treated patients experienced irAEs of any grade, while 11% experienced irAEs of grade 3-5, according to the presented data. In the control arm, 32% experienced irAEs of any grade and 5% experienced grade 3-5 irAEs.

The most common irAEs of any grade were rash, hepatitis, and hypothyroidism, occurring in 28%, 15%, and 12% of atezolizumab-treated patients, respectively.

Median OS in the atezolizumab arm was 25.7 months for patients with irAEs and 13.0 for patients with no irAEs, with a hazard ratio (HR) of 0.69 using a time-dependent Cox model.

Median OS in the control arm was 20.2 months for patients with irAEs and 12.8 months for patients with no irAEs, with an HR of 0.82.

The overall response rate (ORR) in the atezolizumab arm was 61.1% for patients with irAEs and 37.2% for those without irAEs; in the control arm, ORR was 42.2% for patients with irAEs and 34.0% for those with no irAEs.

Atezolizumab-treated patients who experienced grade 3-5 irAEs had the shortest OS, according to Dr. Socinski. The HRs for OS at 1, 3, 6, and 12 months in atezolizumab-treated patients with grade 3-5 irAEs (compared with those without irAEs) ranged from 1.25 to 0.87. By contrast, HRs at those time points for patients with grade 1-2 irAEs ranged from 0.78 to 0.72, Dr. Socinski said.

Dr. Socinski reported disclosures related to AstraZeneca/MedImmune, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Genentech, Guardant Health, Janssen, Lilly, Merck, Novartis, Roche/Genentech, and Spectrum Pharmaceuticals. Dr. Redman reported a consulting or advisory role with AstraZeneca.

Experiencing an immune-related adverse event during checkpoint inhibitor treatment may predict outcomes in patients with non-small cell lung cancer, exploratory analyses of phase 3 trials suggest.

Immune-related adverse events (irAEs) were tied to longer overall survival (OS) in exploratory pooled analyses of three phase 3 clinical trials evaluating atezolizumab-based regimens, according to investigator Mark A. Socinski, MD, of AdventHealth Cancer Institute, Orlando, Fla.

Median OS approached 26 months for patients who received first-line atezolizumab and experienced an irAE, compared with just 13 months for those who did not experience an irAE, according to results reported at the American Society of Clinical Oncology Annual Meeting (Abstract 9002).

Atezolizumab-treated patients with grade 3 or greater irAEs had the shortest OS, shorter than those atezolizumab-treated patients who experienced grade 1-2 irAEs or no irAEs at all. That short OS may be due to treatment interruptions or discontinuations, said Dr. Socinski.

“Data from these analyses suggest an association between irAEs and efficacy in patients with [non-small cell cancer] NSCLC,” he stated in his presentation of the results.
 

A lot more to learn about irAEs

Similar linkages between irAEs and outcomes were observed in pooled analyses of patients enrolled in the control arms of the phase 3 trials, with a median OS of about 20 months for control patients experiencing an irAE, versus about 13 months for those who did not.

That linkage in the control arm prompted a question from an ASCO attendee about why an effect of irAEs, commonly associated with immune checkpoint inhibitor therapy, would be evident in analyses of patients who did not receive those agents.

In his response, Dr. Socinski characterized the finding as “a surprise” and said the finding may either reflect how adverse events are characterized or how chemotherapy impacts the immune system.

“I don’t know that our definition of irAEs is perfect,” he said, “and maybe we don’t understand what impact chemotherapy may have on the immune system, and may actually engender what historically we’ve always seen as an adverse event, but didn’t necessarily classify as an immune-related adverse event.”

More work is needed to better understand the connection between irAES and outcomes, and whether anything can be done as a result of that improved understanding, said discussant Mary Weber Redman, PhD.

“The question is, ‘what is actionable?’” added Dr. Redman, a biostatistician at the Fred Hutchinson Cancer Research Center, Seattle.

A firmer understanding of the relationship between irAEs and outcomes could change how clinicians monitor patients for irAEs, lead to better prediction of which patients may experience higher grade irAEs, and ultimately impact treatment selection potentially to avoid those higher grade events, Dr. Redman said in her remarks.

“Doing these types of analyses are quite important, because we have to look at the breadth of information that we have to be able to interpret that and think about what are future questions,” she said in the question-and-answer session accompanying Dr. Socinski’s presentation.

“I think the key is that we shouldn’t use these analyses to be definitive, but we should use them as to be hypothesis generating,” she added.
 

More evidence to link irAEs and outcomes

Immune-related AEs caused by off-target immune and inflammatory activity have been reported in up to 80% of patients receiving immune checkpoint inhibitors as monotherapy and up to 95% in combination regimens, Dr. Socinski said in his presentation.

“Increasing evidence suggests that the occurrence of immune-related adverse events with PD-L1 or PD-1 inhibitor therapy may be predictive of improved outcomes in cancers such as NSCLC, “ he added.

In their exploratory pooled analyses, Dr. Socinski and co-investigators looked at data from the phase 3 IMpower130 and IMpower132 trials, which evaluated first-line atezolizumab and chemotherapy for NSCLC, and the phase 3 IMpower150 trial, which evaluated atezolizumab plus chemotherapy with or without bevacizumab.

In all, they analyzed data for 1,557 atezolizumab-treated patients, and 900 patients who had been in the control arms of the studies.

Forty-eight percent of atezolizumab-treated patients experienced irAEs of any grade, while 11% experienced irAEs of grade 3-5, according to the presented data. In the control arm, 32% experienced irAEs of any grade and 5% experienced grade 3-5 irAEs.

The most common irAEs of any grade were rash, hepatitis, and hypothyroidism, occurring in 28%, 15%, and 12% of atezolizumab-treated patients, respectively.

Median OS in the atezolizumab arm was 25.7 months for patients with irAEs and 13.0 for patients with no irAEs, with a hazard ratio (HR) of 0.69 using a time-dependent Cox model.

Median OS in the control arm was 20.2 months for patients with irAEs and 12.8 months for patients with no irAEs, with an HR of 0.82.

The overall response rate (ORR) in the atezolizumab arm was 61.1% for patients with irAEs and 37.2% for those without irAEs; in the control arm, ORR was 42.2% for patients with irAEs and 34.0% for those with no irAEs.

Atezolizumab-treated patients who experienced grade 3-5 irAEs had the shortest OS, according to Dr. Socinski. The HRs for OS at 1, 3, 6, and 12 months in atezolizumab-treated patients with grade 3-5 irAEs (compared with those without irAEs) ranged from 1.25 to 0.87. By contrast, HRs at those time points for patients with grade 1-2 irAEs ranged from 0.78 to 0.72, Dr. Socinski said.

Dr. Socinski reported disclosures related to AstraZeneca/MedImmune, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Genentech, Guardant Health, Janssen, Lilly, Merck, Novartis, Roche/Genentech, and Spectrum Pharmaceuticals. Dr. Redman reported a consulting or advisory role with AstraZeneca.

Experiencing an immune-related adverse event during checkpoint inhibitor treatment may predict outcomes in patients with non-small cell lung cancer, exploratory analyses of phase 3 trials suggest.

Immune-related adverse events (irAEs) were tied to longer overall survival (OS) in exploratory pooled analyses of three phase 3 clinical trials evaluating atezolizumab-based regimens, according to investigator Mark A. Socinski, MD, of AdventHealth Cancer Institute, Orlando, Fla.

Median OS approached 26 months for patients who received first-line atezolizumab and experienced an irAE, compared with just 13 months for those who did not experience an irAE, according to results reported at the American Society of Clinical Oncology Annual Meeting (Abstract 9002).

Atezolizumab-treated patients with grade 3 or greater irAEs had the shortest OS, shorter than those atezolizumab-treated patients who experienced grade 1-2 irAEs or no irAEs at all. That short OS may be due to treatment interruptions or discontinuations, said Dr. Socinski.

“Data from these analyses suggest an association between irAEs and efficacy in patients with [non-small cell cancer] NSCLC,” he stated in his presentation of the results.
 

A lot more to learn about irAEs

Similar linkages between irAEs and outcomes were observed in pooled analyses of patients enrolled in the control arms of the phase 3 trials, with a median OS of about 20 months for control patients experiencing an irAE, versus about 13 months for those who did not.

That linkage in the control arm prompted a question from an ASCO attendee about why an effect of irAEs, commonly associated with immune checkpoint inhibitor therapy, would be evident in analyses of patients who did not receive those agents.

In his response, Dr. Socinski characterized the finding as “a surprise” and said the finding may either reflect how adverse events are characterized or how chemotherapy impacts the immune system.

“I don’t know that our definition of irAEs is perfect,” he said, “and maybe we don’t understand what impact chemotherapy may have on the immune system, and may actually engender what historically we’ve always seen as an adverse event, but didn’t necessarily classify as an immune-related adverse event.”

More work is needed to better understand the connection between irAES and outcomes, and whether anything can be done as a result of that improved understanding, said discussant Mary Weber Redman, PhD.

“The question is, ‘what is actionable?’” added Dr. Redman, a biostatistician at the Fred Hutchinson Cancer Research Center, Seattle.

A firmer understanding of the relationship between irAEs and outcomes could change how clinicians monitor patients for irAEs, lead to better prediction of which patients may experience higher grade irAEs, and ultimately impact treatment selection potentially to avoid those higher grade events, Dr. Redman said in her remarks.

“Doing these types of analyses are quite important, because we have to look at the breadth of information that we have to be able to interpret that and think about what are future questions,” she said in the question-and-answer session accompanying Dr. Socinski’s presentation.

“I think the key is that we shouldn’t use these analyses to be definitive, but we should use them as to be hypothesis generating,” she added.
 

More evidence to link irAEs and outcomes

Immune-related AEs caused by off-target immune and inflammatory activity have been reported in up to 80% of patients receiving immune checkpoint inhibitors as monotherapy and up to 95% in combination regimens, Dr. Socinski said in his presentation.

“Increasing evidence suggests that the occurrence of immune-related adverse events with PD-L1 or PD-1 inhibitor therapy may be predictive of improved outcomes in cancers such as NSCLC, “ he added.

In their exploratory pooled analyses, Dr. Socinski and co-investigators looked at data from the phase 3 IMpower130 and IMpower132 trials, which evaluated first-line atezolizumab and chemotherapy for NSCLC, and the phase 3 IMpower150 trial, which evaluated atezolizumab plus chemotherapy with or without bevacizumab.

In all, they analyzed data for 1,557 atezolizumab-treated patients, and 900 patients who had been in the control arms of the studies.

Forty-eight percent of atezolizumab-treated patients experienced irAEs of any grade, while 11% experienced irAEs of grade 3-5, according to the presented data. In the control arm, 32% experienced irAEs of any grade and 5% experienced grade 3-5 irAEs.

The most common irAEs of any grade were rash, hepatitis, and hypothyroidism, occurring in 28%, 15%, and 12% of atezolizumab-treated patients, respectively.

Median OS in the atezolizumab arm was 25.7 months for patients with irAEs and 13.0 for patients with no irAEs, with a hazard ratio (HR) of 0.69 using a time-dependent Cox model.

Median OS in the control arm was 20.2 months for patients with irAEs and 12.8 months for patients with no irAEs, with an HR of 0.82.

The overall response rate (ORR) in the atezolizumab arm was 61.1% for patients with irAEs and 37.2% for those without irAEs; in the control arm, ORR was 42.2% for patients with irAEs and 34.0% for those with no irAEs.

Atezolizumab-treated patients who experienced grade 3-5 irAEs had the shortest OS, according to Dr. Socinski. The HRs for OS at 1, 3, 6, and 12 months in atezolizumab-treated patients with grade 3-5 irAEs (compared with those without irAEs) ranged from 1.25 to 0.87. By contrast, HRs at those time points for patients with grade 1-2 irAEs ranged from 0.78 to 0.72, Dr. Socinski said.

Dr. Socinski reported disclosures related to AstraZeneca/MedImmune, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Genentech, Guardant Health, Janssen, Lilly, Merck, Novartis, Roche/Genentech, and Spectrum Pharmaceuticals. Dr. Redman reported a consulting or advisory role with AstraZeneca.