Key clinical point: The overall incidence of cutaneous adverse events (AEs) was low and manageable, rarely needing treatment cessation, in patients with advanced hormone receptor-positive, human epidermal growth receptor 2-negative breast cancer (HR+HER2−BC) receiving palbociclib and endocrine therapy (ET).

Major finding: The incidence of treatment-related cutaneous AEs was 14.2%, of which only 15.0% and 4.0% required temporary treatment suspension and discontinuation, respectively. The mean time to AE onset was 168 days (6 cycles) of treatment.

Study details: Findings are from a retrospective analysis of 324 adult patients with advanced HR+HER2−BC who received oral palbociclib (mean treatment cycles, 9) and ET.

Disclosures: This study did not declare any specific funding. The authors declared no conflicts of interest.

Source: Chawla S et al. Breast Cancer Res Treat. 2021 Mar 8. doi: 10.1007/s10549-021-06169-9.

Key clinical point: The overall incidence of cutaneous adverse events (AEs) was low and manageable, rarely needing treatment cessation, in patients with advanced hormone receptor-positive, human epidermal growth receptor 2-negative breast cancer (HR+HER2−BC) receiving palbociclib and endocrine therapy (ET).

Major finding: The incidence of treatment-related cutaneous AEs was 14.2%, of which only 15.0% and 4.0% required temporary treatment suspension and discontinuation, respectively. The mean time to AE onset was 168 days (6 cycles) of treatment.

Study details: Findings are from a retrospective analysis of 324 adult patients with advanced HR+HER2−BC who received oral palbociclib (mean treatment cycles, 9) and ET.

Disclosures: This study did not declare any specific funding. The authors declared no conflicts of interest.

Source: Chawla S et al. Breast Cancer Res Treat. 2021 Mar 8. doi: 10.1007/s10549-021-06169-9.

Key clinical point: The overall incidence of cutaneous adverse events (AEs) was low and manageable, rarely needing treatment cessation, in patients with advanced hormone receptor-positive, human epidermal growth receptor 2-negative breast cancer (HR+HER2−BC) receiving palbociclib and endocrine therapy (ET).

Major finding: The incidence of treatment-related cutaneous AEs was 14.2%, of which only 15.0% and 4.0% required temporary treatment suspension and discontinuation, respectively. The mean time to AE onset was 168 days (6 cycles) of treatment.

Study details: Findings are from a retrospective analysis of 324 adult patients with advanced HR+HER2−BC who received oral palbociclib (mean treatment cycles, 9) and ET.

Disclosures: This study did not declare any specific funding. The authors declared no conflicts of interest.

Source: Chawla S et al. Breast Cancer Res Treat. 2021 Mar 8. doi: 10.1007/s10549-021-06169-9.

Key clinical point: Adjuvant endocrine therapy (ET) was associated with improved overall survival (OS) in older patients with node-negative, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2−) invasive breast cancer with multiple comorbidities.

Major finding: During median follow-up of 43.6 months, median OS was higher in patients who received ET vs. those who did not (79.2 months vs. 67.7 months; P less than .0001).

Study details: Findings are from a retrospective, matched cohort analysis of 1,972 older patients (age, 70 years or more) with Charlson/Deyo comorbidity scores of 2 or 3 who received breast and axillary surgery for ER+/HER2−, pathologic node-negative breast cancer.

Disclosures: This work was partly supported by the National Cancer Institute. MS Karuturi reported support from Pfizer. The remaining authors had no disclosures.

Source: Tamirisa N et al. Cancer. 2021 Mar 18. doi: 10.1002/cncr.33489.

Key clinical point: Adjuvant endocrine therapy (ET) was associated with improved overall survival (OS) in older patients with node-negative, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2−) invasive breast cancer with multiple comorbidities.

Major finding: During median follow-up of 43.6 months, median OS was higher in patients who received ET vs. those who did not (79.2 months vs. 67.7 months; P less than .0001).

Study details: Findings are from a retrospective, matched cohort analysis of 1,972 older patients (age, 70 years or more) with Charlson/Deyo comorbidity scores of 2 or 3 who received breast and axillary surgery for ER+/HER2−, pathologic node-negative breast cancer.

Disclosures: This work was partly supported by the National Cancer Institute. MS Karuturi reported support from Pfizer. The remaining authors had no disclosures.

Source: Tamirisa N et al. Cancer. 2021 Mar 18. doi: 10.1002/cncr.33489.

Key clinical point: Adjuvant endocrine therapy (ET) was associated with improved overall survival (OS) in older patients with node-negative, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2−) invasive breast cancer with multiple comorbidities.

Major finding: During median follow-up of 43.6 months, median OS was higher in patients who received ET vs. those who did not (79.2 months vs. 67.7 months; P less than .0001).

Study details: Findings are from a retrospective, matched cohort analysis of 1,972 older patients (age, 70 years or more) with Charlson/Deyo comorbidity scores of 2 or 3 who received breast and axillary surgery for ER+/HER2−, pathologic node-negative breast cancer.

Disclosures: This work was partly supported by the National Cancer Institute. MS Karuturi reported support from Pfizer. The remaining authors had no disclosures.

Source: Tamirisa N et al. Cancer. 2021 Mar 18. doi: 10.1002/cncr.33489.

Key clinical point: Pembrolizumab monotherapy as second- or third-line treatment did not improve overall survival (OS) in patients with previously treated metastatic triple-negative breast cancer (TNBC) compared with chemotherapy.

Major finding: Median OS was similar with pembrolizumab vs. chemotherapy in patients with programmed death-ligand 1 combined positive score of 1 or more (10.7 months vs. 10.2 months; P = .073) or 10 or more (12.7 months vs. 11.6 months; P = .057). Dose modification, reduction, interruption, or withdrawal because of adverse events was lower in pembrolizumab (21%) vs. chemotherapy (45%) groups.

Study details: Findings are from phase 3 KEYNOTE-119 trial including 622 patients with metastatic TNBC who underwent 1 or 2 previous treatments, experienced progression on most recent therapy, and received previous treatment with an anthracycline or taxane. Patients were randomly allocated to receive either intravenous pembrolizumab (n=312) or investigator-choice chemotherapy (n=310).

Disclosures: This study was funded by Merck Sharp and Dohme. Some investigators, including the lead author, reported ties with various pharmaceutical companies including Merck Sharp and Dohme.

Source: Winer EP et al. Lancet Oncol. 2021 Mar 4. doi: 10.1016/S1470-2045(20)30754-3.

Key clinical point: Pembrolizumab monotherapy as second- or third-line treatment did not improve overall survival (OS) in patients with previously treated metastatic triple-negative breast cancer (TNBC) compared with chemotherapy.

Major finding: Median OS was similar with pembrolizumab vs. chemotherapy in patients with programmed death-ligand 1 combined positive score of 1 or more (10.7 months vs. 10.2 months; P = .073) or 10 or more (12.7 months vs. 11.6 months; P = .057). Dose modification, reduction, interruption, or withdrawal because of adverse events was lower in pembrolizumab (21%) vs. chemotherapy (45%) groups.

Study details: Findings are from phase 3 KEYNOTE-119 trial including 622 patients with metastatic TNBC who underwent 1 or 2 previous treatments, experienced progression on most recent therapy, and received previous treatment with an anthracycline or taxane. Patients were randomly allocated to receive either intravenous pembrolizumab (n=312) or investigator-choice chemotherapy (n=310).

Disclosures: This study was funded by Merck Sharp and Dohme. Some investigators, including the lead author, reported ties with various pharmaceutical companies including Merck Sharp and Dohme.

Source: Winer EP et al. Lancet Oncol. 2021 Mar 4. doi: 10.1016/S1470-2045(20)30754-3.

Key clinical point: Pembrolizumab monotherapy as second- or third-line treatment did not improve overall survival (OS) in patients with previously treated metastatic triple-negative breast cancer (TNBC) compared with chemotherapy.

Major finding: Median OS was similar with pembrolizumab vs. chemotherapy in patients with programmed death-ligand 1 combined positive score of 1 or more (10.7 months vs. 10.2 months; P = .073) or 10 or more (12.7 months vs. 11.6 months; P = .057). Dose modification, reduction, interruption, or withdrawal because of adverse events was lower in pembrolizumab (21%) vs. chemotherapy (45%) groups.

Study details: Findings are from phase 3 KEYNOTE-119 trial including 622 patients with metastatic TNBC who underwent 1 or 2 previous treatments, experienced progression on most recent therapy, and received previous treatment with an anthracycline or taxane. Patients were randomly allocated to receive either intravenous pembrolizumab (n=312) or investigator-choice chemotherapy (n=310).

Disclosures: This study was funded by Merck Sharp and Dohme. Some investigators, including the lead author, reported ties with various pharmaceutical companies including Merck Sharp and Dohme.

Source: Winer EP et al. Lancet Oncol. 2021 Mar 4. doi: 10.1016/S1470-2045(20)30754-3.

Key clinical point: Among women with breast cancer and high clinical risk, a subgroup of patients with low genomic risk identified by the 70-gene signature showed excellent distant metastasis-free survival (DMFS) even without chemotherapy. No benefits of chemotherapy were observed in women older than 50 years.

Major finding: Eight-year DMFS in patients with high clinical but low genomic risk with vs. without chemotherapy was 92.0% vs. 89.4%, with the benefit of adding chemotherapy to endocrine therapy remaining small (absolute difference, 2·6 percentage points). Chemotherapy showed no benefits in older women aged more than 50 years (absolute difference, 0.2 percentage points).

Study details: Findings are from the 8-year analysis of phase 3 MINDACT trial, including women with primary nonmetastatic invasive breast cancer with up to 3 positive lymph nodes. The 70-gene signature (MammaPrint) identified women with high clinical but low genomic risk who were randomly assigned to chemotherapy (n=749) vs. no chemotherapy (n=748).

Disclosures: This study was funded by European Commission Sixth Framework Programme (ECSFP). Some investigators including the lead author reported ties with various pharmaceutical companies and funding agencies including the ECSFP.

Source: Piccart M et al. Lancet Oncol. 2021 Mar 12. doi: 10.1016/S1470-2045(21)00007-3.

Key clinical point: Among women with breast cancer and high clinical risk, a subgroup of patients with low genomic risk identified by the 70-gene signature showed excellent distant metastasis-free survival (DMFS) even without chemotherapy. No benefits of chemotherapy were observed in women older than 50 years.

Major finding: Eight-year DMFS in patients with high clinical but low genomic risk with vs. without chemotherapy was 92.0% vs. 89.4%, with the benefit of adding chemotherapy to endocrine therapy remaining small (absolute difference, 2·6 percentage points). Chemotherapy showed no benefits in older women aged more than 50 years (absolute difference, 0.2 percentage points).

Study details: Findings are from the 8-year analysis of phase 3 MINDACT trial, including women with primary nonmetastatic invasive breast cancer with up to 3 positive lymph nodes. The 70-gene signature (MammaPrint) identified women with high clinical but low genomic risk who were randomly assigned to chemotherapy (n=749) vs. no chemotherapy (n=748).

Disclosures: This study was funded by European Commission Sixth Framework Programme (ECSFP). Some investigators including the lead author reported ties with various pharmaceutical companies and funding agencies including the ECSFP.

Source: Piccart M et al. Lancet Oncol. 2021 Mar 12. doi: 10.1016/S1470-2045(21)00007-3.

Key clinical point: Among women with breast cancer and high clinical risk, a subgroup of patients with low genomic risk identified by the 70-gene signature showed excellent distant metastasis-free survival (DMFS) even without chemotherapy. No benefits of chemotherapy were observed in women older than 50 years.

Major finding: Eight-year DMFS in patients with high clinical but low genomic risk with vs. without chemotherapy was 92.0% vs. 89.4%, with the benefit of adding chemotherapy to endocrine therapy remaining small (absolute difference, 2·6 percentage points). Chemotherapy showed no benefits in older women aged more than 50 years (absolute difference, 0.2 percentage points).

Study details: Findings are from the 8-year analysis of phase 3 MINDACT trial, including women with primary nonmetastatic invasive breast cancer with up to 3 positive lymph nodes. The 70-gene signature (MammaPrint) identified women with high clinical but low genomic risk who were randomly assigned to chemotherapy (n=749) vs. no chemotherapy (n=748).

Disclosures: This study was funded by European Commission Sixth Framework Programme (ECSFP). Some investigators including the lead author reported ties with various pharmaceutical companies and funding agencies including the ECSFP.

Source: Piccart M et al. Lancet Oncol. 2021 Mar 12. doi: 10.1016/S1470-2045(21)00007-3.

Key clinical point: Among women with breast cancer and high clinical risk, a subgroup of patients with low genomic risk identified by the 70-gene signature showed excellent distant metastasis-free survival (DMFS) even without chemotherapy. No benefits of chemotherapy were observed in women older than 50 years.

Major finding: Eight-year DMFS in patients with high clinical but low genomic risk with vs. without chemotherapy was 92.0% vs. 89.4%, with the benefit of adding chemotherapy to endocrine therapy remaining small (absolute difference, 2·6 percentage points). Chemotherapy showed no benefits in older women aged more than 50 years (absolute difference, 0.2 percentage points).

Study details: Findings are from the 8-year analysis of phase 3 MINDACT trial, including women with primary nonmetastatic invasive breast cancer with up to 3 positive lymph nodes. The 70-gene signature (MammaPrint) identified women with high clinical but low genomic risk who were randomly assigned to chemotherapy (n=749) vs. no chemotherapy (n=748).

Disclosures: This study was funded by European Commission Sixth Framework Programme (ECSFP). Some investigators including the lead author reported ties with various pharmaceutical companies and funding agencies including the ECSFP.

Source: Piccart M et al. Lancet Oncol. 2021 Mar 12. doi: 10.1016/S1470-2045(21)00007-3.

Key clinical point: Among women with breast cancer and high clinical risk, a subgroup of patients with low genomic risk identified by the 70-gene signature showed excellent distant metastasis-free survival (DMFS) even without chemotherapy. No benefits of chemotherapy were observed in women older than 50 years.

Major finding: Eight-year DMFS in patients with high clinical but low genomic risk with vs. without chemotherapy was 92.0% vs. 89.4%, with the benefit of adding chemotherapy to endocrine therapy remaining small (absolute difference, 2·6 percentage points). Chemotherapy showed no benefits in older women aged more than 50 years (absolute difference, 0.2 percentage points).

Study details: Findings are from the 8-year analysis of phase 3 MINDACT trial, including women with primary nonmetastatic invasive breast cancer with up to 3 positive lymph nodes. The 70-gene signature (MammaPrint) identified women with high clinical but low genomic risk who were randomly assigned to chemotherapy (n=749) vs. no chemotherapy (n=748).

Disclosures: This study was funded by European Commission Sixth Framework Programme (ECSFP). Some investigators including the lead author reported ties with various pharmaceutical companies and funding agencies including the ECSFP.

Source: Piccart M et al. Lancet Oncol. 2021 Mar 12. doi: 10.1016/S1470-2045(21)00007-3.

Key clinical point: Among women with breast cancer and high clinical risk, a subgroup of patients with low genomic risk identified by the 70-gene signature showed excellent distant metastasis-free survival (DMFS) even without chemotherapy. No benefits of chemotherapy were observed in women older than 50 years.

Major finding: Eight-year DMFS in patients with high clinical but low genomic risk with vs. without chemotherapy was 92.0% vs. 89.4%, with the benefit of adding chemotherapy to endocrine therapy remaining small (absolute difference, 2·6 percentage points). Chemotherapy showed no benefits in older women aged more than 50 years (absolute difference, 0.2 percentage points).

Study details: Findings are from the 8-year analysis of phase 3 MINDACT trial, including women with primary nonmetastatic invasive breast cancer with up to 3 positive lymph nodes. The 70-gene signature (MammaPrint) identified women with high clinical but low genomic risk who were randomly assigned to chemotherapy (n=749) vs. no chemotherapy (n=748).

Disclosures: This study was funded by European Commission Sixth Framework Programme (ECSFP). Some investigators including the lead author reported ties with various pharmaceutical companies and funding agencies including the ECSFP.

Source: Piccart M et al. Lancet Oncol. 2021 Mar 12. doi: 10.1016/S1470-2045(21)00007-3.

In a new randomized trial that investigated the question of whether thrombolysis can be omitted for patients with stroke who are undergoing endovascular thrombectomy for a large-vessel occlusion, results were similar for both approaches.

The MR CLEAN NO IV trial failed to show superiority or noninferiority of direct endovascular treatment over intravenous alteplase (tissue plasminogen activator, tPA) followed by endovascular treatment, and functional outcomes were not significantly different. In addition, hemorrhage rates with or without intravenous alteplase administration before endovascular treatment were similar.

“From the MR CLEAN NO IV results, we cannot change standard practice, as we failed to show superiority of the direct endovascular approach, and we also didn’t meet the noninferiority criteria. So, the standard practice of giving tPA to those eligible still holds,” said co–lead investigator Yvo Roos, MD.

“But I think we can say that these results suggest that there may also not be such a need for tPA in patients who can go straight for endovascular therapy,” said Dr. Roos, who is professor of neurology at Amsterdam Medical Center.

“If we are not sure whether a patient is suitable for tPA because they have a higher bleeding risk, I think we can be reassured about missing the tPA out and going straight to endovascular treatment. So, if in doubt, leave it out,” he added.

Results of the MR CLEAN NO IV trial were presented at the International Stroke Conference sponsored by the American Heart Association.
 

“If in doubt, leave it out”

Dr. Roos noted that three trials have investigated the question regarding dropping thrombolysis for patients who can receive thrombectomy quickly. These are the DIRECT MT, SKIP, and DEVT studies. All of these trials were conducted in Asian countries, and none found differences in functional outcomes between the two approaches.

The largest of these studies – the DIRECT-MT trial, from China, which was a sister study to MR CLEAN NO IV – did show noninferiority of the direct endovascular approach to tPA plus endovascular treatment.

But because of differences in health care logistics and trial populations, the benefits and risks of dropping thrombolysis in Western countries are not known, explained Charles Majoie, MD, who is co–lead investigator of the current trial and is chair of neuroradiology at Amsterdam Medical Center.

The MR CLEAN NO IV trial was designed to show superiority of the direct endovascular approach with noninferiority for hemorrhage. It enrolled 540 European patients who were eligible for both thrombolysis and thrombectomy and who presented to a thrombectomy-capable center. They were randomly assigned to receive thrombolysis plus endovascular therapy or direct endovascular therapy alone.

The mean time from stroke onset to groin puncture (the start of endovascular therapy) was very fast in both groups – 130 minutes in the direct group, and 135 minutes in the tPA group.

The primary outcome was a shift analysis of the Modified Rankin Scale (mRS). On that outcome, the trial failed to show significant superiority of the direct approach (odds ratio, 0.88; 95% confidence interval, 0.65-1.19).

A good functional outcome (mRS, 0-2) was achieved in 49% of the direct thrombectomy group and in 51% of the tPA group (OR, 0.95; 95% CI, 0.65-1.40).

Safety results showed no difference in any of the hemorrhage endpoints between the two groups. The rate of symptomatic intracranial hemorrhage was actually numerically higher in the direct thrombectomy group (5.9% vs. 5.3%).

“One of the most intriguing results of this study is that there was no increase in hemorrhage in the tPA group,” Dr. Roos commented. “This is very surprising, as we have always thought thrombolysis causes an increased bleeding risk. But after these results, we may have to rethink that idea – perhaps it is not the tPA itself that causes bleeding risk but rather the opening up of the vessel.”

On the failure to show noninferiority of the direct approach, Dr. Roos suggested that the trial may have been underpowered in this respect.

“Our sister trial, DIRECT-MT, was a noninferiority study. They had 650 patients, and they just reached noninferiority,” he said. “In MR CLEAN NO IV, we were aiming for superiority, and we had fewer patients – 540. We didn’t show superiority, and we didn’t have quite enough patients to show noninferiority.”

He added that, considering all the four studies together, the results look very similar and suggest no difference between the two approaches.
 

Individualized approach probable

Dr. Majoie suggested that different patients may be suitable for the different approaches.

“I think we are heading for individualized treatment. If we have a young patient and the angiography suite is ready, we could probably skip tPA, but it would be for the neurologist/neuroradiologist to make individualized decisions on this,” he said. “We need to look at subgroups for more information.”

Another large trial that investigated this issue, SWIFT-DIRECT, is expected to be presented later this year. An Australian trial, DIRECT-SAFE, is ongoing and is at an early stage of recruitment.

Dr. Roos said that the data from all the trials will be combined for a more comprehensive analysis of the benefits and risks of the two approaches in various subgroups.

Commenting on the study was cochair of the ISC session at which it was presented, Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, N.J.

“Putting these results together with the previous Asian studies, I think we can say that direct thrombectomy without tPA is clearly not superior to the combined approach of tPA plus thrombectomy,” he said.

Dr. Jovin explained that, in theory, direct thrombectomy could be faster than the combined approach and that the risk for symptomatic intracerebral hemorrhage could be lower. But neither of these two possible benefits were seen in this study.

He agreed with Dr. Roos that MR CLEAN NO IV could have failed to show noninferiority of the direct strategy because the sample was not large enough.

“The results of the two approaches are very similar in this study and in the Asian studies, so it doesn’t appear that tPA adds very much, and it is associated with a significant increase in costs,” he said.

“The answer will probably be that there is not a ‘one-size-fits-all’ strategy, and we may end up using different approaches for different patient groups,” Dr. Jovin added. “Information on this will come from subgroups analyses from these trials.”

MR CLEAN NO-IV trial was part of the CONTRAST consortium, which is supported by the Netherlands Cardiovascular Research Initiative (an initiative of the Dutch Heart Foundation), the Brain Foundation Netherlands, Medtronic, Health-Holland, and Top Sector Life Sciences. The study received additional unrestricted funding from Stryker European Operations. Dr. Roos and Dr. Majoie are shareholders of Nico Lab.

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

In a new randomized trial that investigated the question of whether thrombolysis can be omitted for patients with stroke who are undergoing endovascular thrombectomy for a large-vessel occlusion, results were similar for both approaches.

The MR CLEAN NO IV trial failed to show superiority or noninferiority of direct endovascular treatment over intravenous alteplase (tissue plasminogen activator, tPA) followed by endovascular treatment, and functional outcomes were not significantly different. In addition, hemorrhage rates with or without intravenous alteplase administration before endovascular treatment were similar.

“From the MR CLEAN NO IV results, we cannot change standard practice, as we failed to show superiority of the direct endovascular approach, and we also didn’t meet the noninferiority criteria. So, the standard practice of giving tPA to those eligible still holds,” said co–lead investigator Yvo Roos, MD.

“But I think we can say that these results suggest that there may also not be such a need for tPA in patients who can go straight for endovascular therapy,” said Dr. Roos, who is professor of neurology at Amsterdam Medical Center.

“If we are not sure whether a patient is suitable for tPA because they have a higher bleeding risk, I think we can be reassured about missing the tPA out and going straight to endovascular treatment. So, if in doubt, leave it out,” he added.

Results of the MR CLEAN NO IV trial were presented at the International Stroke Conference sponsored by the American Heart Association.
 

“If in doubt, leave it out”

Dr. Roos noted that three trials have investigated the question regarding dropping thrombolysis for patients who can receive thrombectomy quickly. These are the DIRECT MT, SKIP, and DEVT studies. All of these trials were conducted in Asian countries, and none found differences in functional outcomes between the two approaches.

The largest of these studies – the DIRECT-MT trial, from China, which was a sister study to MR CLEAN NO IV – did show noninferiority of the direct endovascular approach to tPA plus endovascular treatment.

But because of differences in health care logistics and trial populations, the benefits and risks of dropping thrombolysis in Western countries are not known, explained Charles Majoie, MD, who is co–lead investigator of the current trial and is chair of neuroradiology at Amsterdam Medical Center.

The MR CLEAN NO IV trial was designed to show superiority of the direct endovascular approach with noninferiority for hemorrhage. It enrolled 540 European patients who were eligible for both thrombolysis and thrombectomy and who presented to a thrombectomy-capable center. They were randomly assigned to receive thrombolysis plus endovascular therapy or direct endovascular therapy alone.

The mean time from stroke onset to groin puncture (the start of endovascular therapy) was very fast in both groups – 130 minutes in the direct group, and 135 minutes in the tPA group.

The primary outcome was a shift analysis of the Modified Rankin Scale (mRS). On that outcome, the trial failed to show significant superiority of the direct approach (odds ratio, 0.88; 95% confidence interval, 0.65-1.19).

A good functional outcome (mRS, 0-2) was achieved in 49% of the direct thrombectomy group and in 51% of the tPA group (OR, 0.95; 95% CI, 0.65-1.40).

Safety results showed no difference in any of the hemorrhage endpoints between the two groups. The rate of symptomatic intracranial hemorrhage was actually numerically higher in the direct thrombectomy group (5.9% vs. 5.3%).

“One of the most intriguing results of this study is that there was no increase in hemorrhage in the tPA group,” Dr. Roos commented. “This is very surprising, as we have always thought thrombolysis causes an increased bleeding risk. But after these results, we may have to rethink that idea – perhaps it is not the tPA itself that causes bleeding risk but rather the opening up of the vessel.”

On the failure to show noninferiority of the direct approach, Dr. Roos suggested that the trial may have been underpowered in this respect.

“Our sister trial, DIRECT-MT, was a noninferiority study. They had 650 patients, and they just reached noninferiority,” he said. “In MR CLEAN NO IV, we were aiming for superiority, and we had fewer patients – 540. We didn’t show superiority, and we didn’t have quite enough patients to show noninferiority.”

He added that, considering all the four studies together, the results look very similar and suggest no difference between the two approaches.
 

Individualized approach probable

Dr. Majoie suggested that different patients may be suitable for the different approaches.

“I think we are heading for individualized treatment. If we have a young patient and the angiography suite is ready, we could probably skip tPA, but it would be for the neurologist/neuroradiologist to make individualized decisions on this,” he said. “We need to look at subgroups for more information.”

Another large trial that investigated this issue, SWIFT-DIRECT, is expected to be presented later this year. An Australian trial, DIRECT-SAFE, is ongoing and is at an early stage of recruitment.

Dr. Roos said that the data from all the trials will be combined for a more comprehensive analysis of the benefits and risks of the two approaches in various subgroups.

Commenting on the study was cochair of the ISC session at which it was presented, Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, N.J.

“Putting these results together with the previous Asian studies, I think we can say that direct thrombectomy without tPA is clearly not superior to the combined approach of tPA plus thrombectomy,” he said.

Dr. Jovin explained that, in theory, direct thrombectomy could be faster than the combined approach and that the risk for symptomatic intracerebral hemorrhage could be lower. But neither of these two possible benefits were seen in this study.

He agreed with Dr. Roos that MR CLEAN NO IV could have failed to show noninferiority of the direct strategy because the sample was not large enough.

“The results of the two approaches are very similar in this study and in the Asian studies, so it doesn’t appear that tPA adds very much, and it is associated with a significant increase in costs,” he said.

“The answer will probably be that there is not a ‘one-size-fits-all’ strategy, and we may end up using different approaches for different patient groups,” Dr. Jovin added. “Information on this will come from subgroups analyses from these trials.”

MR CLEAN NO-IV trial was part of the CONTRAST consortium, which is supported by the Netherlands Cardiovascular Research Initiative (an initiative of the Dutch Heart Foundation), the Brain Foundation Netherlands, Medtronic, Health-Holland, and Top Sector Life Sciences. The study received additional unrestricted funding from Stryker European Operations. Dr. Roos and Dr. Majoie are shareholders of Nico Lab.

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

In a new randomized trial that investigated the question of whether thrombolysis can be omitted for patients with stroke who are undergoing endovascular thrombectomy for a large-vessel occlusion, results were similar for both approaches.

The MR CLEAN NO IV trial failed to show superiority or noninferiority of direct endovascular treatment over intravenous alteplase (tissue plasminogen activator, tPA) followed by endovascular treatment, and functional outcomes were not significantly different. In addition, hemorrhage rates with or without intravenous alteplase administration before endovascular treatment were similar.

“From the MR CLEAN NO IV results, we cannot change standard practice, as we failed to show superiority of the direct endovascular approach, and we also didn’t meet the noninferiority criteria. So, the standard practice of giving tPA to those eligible still holds,” said co–lead investigator Yvo Roos, MD.

“But I think we can say that these results suggest that there may also not be such a need for tPA in patients who can go straight for endovascular therapy,” said Dr. Roos, who is professor of neurology at Amsterdam Medical Center.

“If we are not sure whether a patient is suitable for tPA because they have a higher bleeding risk, I think we can be reassured about missing the tPA out and going straight to endovascular treatment. So, if in doubt, leave it out,” he added.

Results of the MR CLEAN NO IV trial were presented at the International Stroke Conference sponsored by the American Heart Association.
 

“If in doubt, leave it out”

Dr. Roos noted that three trials have investigated the question regarding dropping thrombolysis for patients who can receive thrombectomy quickly. These are the DIRECT MT, SKIP, and DEVT studies. All of these trials were conducted in Asian countries, and none found differences in functional outcomes between the two approaches.

The largest of these studies – the DIRECT-MT trial, from China, which was a sister study to MR CLEAN NO IV – did show noninferiority of the direct endovascular approach to tPA plus endovascular treatment.

But because of differences in health care logistics and trial populations, the benefits and risks of dropping thrombolysis in Western countries are not known, explained Charles Majoie, MD, who is co–lead investigator of the current trial and is chair of neuroradiology at Amsterdam Medical Center.

The MR CLEAN NO IV trial was designed to show superiority of the direct endovascular approach with noninferiority for hemorrhage. It enrolled 540 European patients who were eligible for both thrombolysis and thrombectomy and who presented to a thrombectomy-capable center. They were randomly assigned to receive thrombolysis plus endovascular therapy or direct endovascular therapy alone.

The mean time from stroke onset to groin puncture (the start of endovascular therapy) was very fast in both groups – 130 minutes in the direct group, and 135 minutes in the tPA group.

The primary outcome was a shift analysis of the Modified Rankin Scale (mRS). On that outcome, the trial failed to show significant superiority of the direct approach (odds ratio, 0.88; 95% confidence interval, 0.65-1.19).

A good functional outcome (mRS, 0-2) was achieved in 49% of the direct thrombectomy group and in 51% of the tPA group (OR, 0.95; 95% CI, 0.65-1.40).

Safety results showed no difference in any of the hemorrhage endpoints between the two groups. The rate of symptomatic intracranial hemorrhage was actually numerically higher in the direct thrombectomy group (5.9% vs. 5.3%).

“One of the most intriguing results of this study is that there was no increase in hemorrhage in the tPA group,” Dr. Roos commented. “This is very surprising, as we have always thought thrombolysis causes an increased bleeding risk. But after these results, we may have to rethink that idea – perhaps it is not the tPA itself that causes bleeding risk but rather the opening up of the vessel.”

On the failure to show noninferiority of the direct approach, Dr. Roos suggested that the trial may have been underpowered in this respect.

“Our sister trial, DIRECT-MT, was a noninferiority study. They had 650 patients, and they just reached noninferiority,” he said. “In MR CLEAN NO IV, we were aiming for superiority, and we had fewer patients – 540. We didn’t show superiority, and we didn’t have quite enough patients to show noninferiority.”

He added that, considering all the four studies together, the results look very similar and suggest no difference between the two approaches.
 

Individualized approach probable

Dr. Majoie suggested that different patients may be suitable for the different approaches.

“I think we are heading for individualized treatment. If we have a young patient and the angiography suite is ready, we could probably skip tPA, but it would be for the neurologist/neuroradiologist to make individualized decisions on this,” he said. “We need to look at subgroups for more information.”

Another large trial that investigated this issue, SWIFT-DIRECT, is expected to be presented later this year. An Australian trial, DIRECT-SAFE, is ongoing and is at an early stage of recruitment.

Dr. Roos said that the data from all the trials will be combined for a more comprehensive analysis of the benefits and risks of the two approaches in various subgroups.

Commenting on the study was cochair of the ISC session at which it was presented, Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, N.J.

“Putting these results together with the previous Asian studies, I think we can say that direct thrombectomy without tPA is clearly not superior to the combined approach of tPA plus thrombectomy,” he said.

Dr. Jovin explained that, in theory, direct thrombectomy could be faster than the combined approach and that the risk for symptomatic intracerebral hemorrhage could be lower. But neither of these two possible benefits were seen in this study.

He agreed with Dr. Roos that MR CLEAN NO IV could have failed to show noninferiority of the direct strategy because the sample was not large enough.

“The results of the two approaches are very similar in this study and in the Asian studies, so it doesn’t appear that tPA adds very much, and it is associated with a significant increase in costs,” he said.

“The answer will probably be that there is not a ‘one-size-fits-all’ strategy, and we may end up using different approaches for different patient groups,” Dr. Jovin added. “Information on this will come from subgroups analyses from these trials.”

MR CLEAN NO-IV trial was part of the CONTRAST consortium, which is supported by the Netherlands Cardiovascular Research Initiative (an initiative of the Dutch Heart Foundation), the Brain Foundation Netherlands, Medtronic, Health-Holland, and Top Sector Life Sciences. The study received additional unrestricted funding from Stryker European Operations. Dr. Roos and Dr. Majoie are shareholders of Nico Lab.

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

Key clinical point: Women vs. men with migraine had a higher frequency of self-reported neck pain and higher prevalence and severity of cutaneous allodynia (CA).

Major finding: Women vs. men showed higher prevalence of self-reported neck pain (73.33% vs. 43.33%; P = .04), CA (P = .001), and 4 times higher risk of having severe CA (P = .007).

Study details: Findings are from a cross-sectional study of 30 men and 30 women with migraine.

Disclosures: The study was supported by a grant from the Fundação de Amparo à Pesquisa do Estado de São Paulo to NDS Xavier. No other conflicts of interest were reported.

Source: Xavier NDS et al. Pain Med. 2021 Mar 19. doi: 10.1093/pm/pnab106.

Key clinical point: Women vs. men with migraine had a higher frequency of self-reported neck pain and higher prevalence and severity of cutaneous allodynia (CA).

Major finding: Women vs. men showed higher prevalence of self-reported neck pain (73.33% vs. 43.33%; P = .04), CA (P = .001), and 4 times higher risk of having severe CA (P = .007).

Study details: Findings are from a cross-sectional study of 30 men and 30 women with migraine.

Disclosures: The study was supported by a grant from the Fundação de Amparo à Pesquisa do Estado de São Paulo to NDS Xavier. No other conflicts of interest were reported.

Source: Xavier NDS et al. Pain Med. 2021 Mar 19. doi: 10.1093/pm/pnab106.

Key clinical point: Women vs. men with migraine had a higher frequency of self-reported neck pain and higher prevalence and severity of cutaneous allodynia (CA).

Major finding: Women vs. men showed higher prevalence of self-reported neck pain (73.33% vs. 43.33%; P = .04), CA (P = .001), and 4 times higher risk of having severe CA (P = .007).

Study details: Findings are from a cross-sectional study of 30 men and 30 women with migraine.

Disclosures: The study was supported by a grant from the Fundação de Amparo à Pesquisa do Estado de São Paulo to NDS Xavier. No other conflicts of interest were reported.

Source: Xavier NDS et al. Pain Med. 2021 Mar 19. doi: 10.1093/pm/pnab106.

Key clinical point: People with migraine may experience a wide range of comorbidities and co-occurring conditions, which should be managed effectively.

Major finding: Patients with vs. without migraine were 3 times more likely to experience insomnia (adjusted odds ratio [aOR], 3.79; 95% confidence interval, [95% CI], 3.6-4.0), depression (aOR, 3.18; 95% CI, 3.0-3.3), anxiety (aOR, 3.18; 95% CI, 3.0-3.3), and gastric ulcer/gastrointestinal bleeding (aOR, 3.11; 95% CI, 2.8-3.5).

Study details: Data come from the prospective, web-based Migraine in America Symptoms and Treatment survey involving adults with (n=15,133) and without migraine (n=77,453).

Disclosures: The study was funded and sponsored by Dr. Reddy’s Laboratories group of companies, Princeton, USA. The lead author along with others declared receiving grant support and/or honoraria from various sources. S Munjal and P Singh declared being employees while RB Lipton, DC Buse, ML Reed, TJ Schwedt, and DW Dodick reported being consultants at Dr. Reddy’s Laboratories.

Source: Buse DC et al. J Headache Pain. 2020 Mar 2. doi: 10.1186/s10194-020-1084-y.

Key clinical point: People with migraine may experience a wide range of comorbidities and co-occurring conditions, which should be managed effectively.

Major finding: Patients with vs. without migraine were 3 times more likely to experience insomnia (adjusted odds ratio [aOR], 3.79; 95% confidence interval, [95% CI], 3.6-4.0), depression (aOR, 3.18; 95% CI, 3.0-3.3), anxiety (aOR, 3.18; 95% CI, 3.0-3.3), and gastric ulcer/gastrointestinal bleeding (aOR, 3.11; 95% CI, 2.8-3.5).

Study details: Data come from the prospective, web-based Migraine in America Symptoms and Treatment survey involving adults with (n=15,133) and without migraine (n=77,453).

Disclosures: The study was funded and sponsored by Dr. Reddy’s Laboratories group of companies, Princeton, USA. The lead author along with others declared receiving grant support and/or honoraria from various sources. S Munjal and P Singh declared being employees while RB Lipton, DC Buse, ML Reed, TJ Schwedt, and DW Dodick reported being consultants at Dr. Reddy’s Laboratories.

Source: Buse DC et al. J Headache Pain. 2020 Mar 2. doi: 10.1186/s10194-020-1084-y.

Key clinical point: People with migraine may experience a wide range of comorbidities and co-occurring conditions, which should be managed effectively.

Major finding: Patients with vs. without migraine were 3 times more likely to experience insomnia (adjusted odds ratio [aOR], 3.79; 95% confidence interval, [95% CI], 3.6-4.0), depression (aOR, 3.18; 95% CI, 3.0-3.3), anxiety (aOR, 3.18; 95% CI, 3.0-3.3), and gastric ulcer/gastrointestinal bleeding (aOR, 3.11; 95% CI, 2.8-3.5).

Study details: Data come from the prospective, web-based Migraine in America Symptoms and Treatment survey involving adults with (n=15,133) and without migraine (n=77,453).

Disclosures: The study was funded and sponsored by Dr. Reddy’s Laboratories group of companies, Princeton, USA. The lead author along with others declared receiving grant support and/or honoraria from various sources. S Munjal and P Singh declared being employees while RB Lipton, DC Buse, ML Reed, TJ Schwedt, and DW Dodick reported being consultants at Dr. Reddy’s Laboratories.

Source: Buse DC et al. J Headache Pain. 2020 Mar 2. doi: 10.1186/s10194-020-1084-y.

Key clinical point: Addition of a calcitonin gene-related peptide (CGRP)-targeted monoclonal antibodies (mAbs) in patients with chronic migraine (CM) receiving onabotulinumtoxinA (onabot) resulted in further reductions in monthly headache days (MHDs) without major tolerability issues.

Major finding: Patients reported an average decrease of 10.9 MHDs (P less than .001) after onabot treatment and a further decrease of 5.7 MHDs (P less than .001) after addition of CGRP-targeted mAbs resulting in a total decrease of 16.6 MHDs (P less than .001) with combined therapy. No serious adverse events were reported.

Study details: The data come from a retrospective review of 153 patients with CM receiving onabot and subsequently prescribed CGRP-targeted mAbs.

Disclosures: The study did not receive any funding. The lead author F Cohen reported no conflicts of interest. The other authors declared receiving honoraria and research support from various sources and serving as consultant and/or advisory board member for various pharmaceutical companies.

Source: Cohen F et al. Pain Med. 2021 Mar 8. doi: 10.1093/pm/pnab093.

Key clinical point: Addition of a calcitonin gene-related peptide (CGRP)-targeted monoclonal antibodies (mAbs) in patients with chronic migraine (CM) receiving onabotulinumtoxinA (onabot) resulted in further reductions in monthly headache days (MHDs) without major tolerability issues.

Major finding: Patients reported an average decrease of 10.9 MHDs (P less than .001) after onabot treatment and a further decrease of 5.7 MHDs (P less than .001) after addition of CGRP-targeted mAbs resulting in a total decrease of 16.6 MHDs (P less than .001) with combined therapy. No serious adverse events were reported.

Study details: The data come from a retrospective review of 153 patients with CM receiving onabot and subsequently prescribed CGRP-targeted mAbs.

Disclosures: The study did not receive any funding. The lead author F Cohen reported no conflicts of interest. The other authors declared receiving honoraria and research support from various sources and serving as consultant and/or advisory board member for various pharmaceutical companies.

Source: Cohen F et al. Pain Med. 2021 Mar 8. doi: 10.1093/pm/pnab093.

Key clinical point: Addition of a calcitonin gene-related peptide (CGRP)-targeted monoclonal antibodies (mAbs) in patients with chronic migraine (CM) receiving onabotulinumtoxinA (onabot) resulted in further reductions in monthly headache days (MHDs) without major tolerability issues.

Major finding: Patients reported an average decrease of 10.9 MHDs (P less than .001) after onabot treatment and a further decrease of 5.7 MHDs (P less than .001) after addition of CGRP-targeted mAbs resulting in a total decrease of 16.6 MHDs (P less than .001) with combined therapy. No serious adverse events were reported.

Study details: The data come from a retrospective review of 153 patients with CM receiving onabot and subsequently prescribed CGRP-targeted mAbs.

Disclosures: The study did not receive any funding. The lead author F Cohen reported no conflicts of interest. The other authors declared receiving honoraria and research support from various sources and serving as consultant and/or advisory board member for various pharmaceutical companies.

Source: Cohen F et al. Pain Med. 2021 Mar 8. doi: 10.1093/pm/pnab093.

Key clinical point: Intravenous eptinezumab demonstrated a favorable safety profile in patients with chronic migraine (CM).

Major finding: Overall, 71.1% of patients experienced 1 or more treatment-emergent adverse events (TEAEs) during the entire 2 years of study duration with majority (95.6%) being mild or moderate. TEAEs leading to drug discontinuation or withdrawal were observed in only 7.8% and 6.3% of patients, respectively. Incidence of serious TEAEs and drug-related AEs was low.

Study details: PREVAIL, an open-label phase 3 trial, included 128 adults with CM who received at least 1 dose of eptinezumab (300 mg) every 12 weeks for up to 8 doses.

Disclosures: This study was funded by H. Lundbeck A/S, Copenhagen, Denmark. D Kudrow reported receiving grant support from, being on advisory board, and/or being speaker for multiple sources. Some of the authors reported being current/former full-time employees at Lundbeck Seattle BioPharmaceuticals or Alder Biopharmaceuticals (CKA Lundbeck Seattle Biopharmaceuticals, Inc).

Source: Kudrow D et al. BMC Neurol. 2021 Mar 19. doi: 10.1186/s12883-021-02123-w.

Key clinical point: Intravenous eptinezumab demonstrated a favorable safety profile in patients with chronic migraine (CM).

Major finding: Overall, 71.1% of patients experienced 1 or more treatment-emergent adverse events (TEAEs) during the entire 2 years of study duration with majority (95.6%) being mild or moderate. TEAEs leading to drug discontinuation or withdrawal were observed in only 7.8% and 6.3% of patients, respectively. Incidence of serious TEAEs and drug-related AEs was low.

Study details: PREVAIL, an open-label phase 3 trial, included 128 adults with CM who received at least 1 dose of eptinezumab (300 mg) every 12 weeks for up to 8 doses.

Disclosures: This study was funded by H. Lundbeck A/S, Copenhagen, Denmark. D Kudrow reported receiving grant support from, being on advisory board, and/or being speaker for multiple sources. Some of the authors reported being current/former full-time employees at Lundbeck Seattle BioPharmaceuticals or Alder Biopharmaceuticals (CKA Lundbeck Seattle Biopharmaceuticals, Inc).

Source: Kudrow D et al. BMC Neurol. 2021 Mar 19. doi: 10.1186/s12883-021-02123-w.

Key clinical point: Intravenous eptinezumab demonstrated a favorable safety profile in patients with chronic migraine (CM).

Major finding: Overall, 71.1% of patients experienced 1 or more treatment-emergent adverse events (TEAEs) during the entire 2 years of study duration with majority (95.6%) being mild or moderate. TEAEs leading to drug discontinuation or withdrawal were observed in only 7.8% and 6.3% of patients, respectively. Incidence of serious TEAEs and drug-related AEs was low.

Study details: PREVAIL, an open-label phase 3 trial, included 128 adults with CM who received at least 1 dose of eptinezumab (300 mg) every 12 weeks for up to 8 doses.

Disclosures: This study was funded by H. Lundbeck A/S, Copenhagen, Denmark. D Kudrow reported receiving grant support from, being on advisory board, and/or being speaker for multiple sources. Some of the authors reported being current/former full-time employees at Lundbeck Seattle BioPharmaceuticals or Alder Biopharmaceuticals (CKA Lundbeck Seattle Biopharmaceuticals, Inc).

Source: Kudrow D et al. BMC Neurol. 2021 Mar 19. doi: 10.1186/s12883-021-02123-w.