Top-line results from a phase 2 study suggest vixotrigine (BIIB074, Biogen), a nonopioid investigational oral pain medication, reduces chronic neuropathic pain caused by small fiber neuropathy (SFN) and is generally well tolerated.

“We are encouraged by the overall results of the CONVEY study, especially given the significant unmet medical need for additional agents to treat chronic painful neuropathy,” Katherine Dawson, MD, senior vice president and head of the therapeutics development unit at Biogen, said in a news release.

Vixotrigine (BIIB074) is a peripherally and centrally acting, orally administered, voltage- and use-dependent voltage-gated sodium channel blocker.

CONVEY was a phase 2, placebo-controlled, double-blind, randomized withdrawal study of 265 patients experiencing pain from confirmed idiopathic or diabetes-associated SFN.

Following a 4-week open-label run-in period, 123 responders to vixotrigine were randomly allocated to 200 mg or 350 mg vixotrigine or placebo twice daily for 12 weeks in the double-blind portion of the study.

At week 12, vixotrigine 200 mg twice daily met the primary endpoint of a statistically significant reduction from baseline in the mean average daily pain (ADP) score versus placebo (P = .0501).

A subgroup analysis showed a treatment effect in patients with diabetes-associated SFN but not in the smaller subgroup of patients with idiopathic SFN.

The 200-mg dose also led to a significant improvement over placebo in mean worst daily pain score at 12 weeks (P = .0455).

A numeric advantage of 200 mg vixotrigine over placebo was observed in additional secondary endpoints, including the proportion of patients with at least a 2-point improvement in ADP score and the proportion with at least a 30% reduction in ADP at week 12, but these failed to reach statistical significance.

Vixotrigine 350 mg twice daily did not meet the primary endpoint of mean change in ADP at 12 weeks.

However, treatment at the higher dose led to a significant increase in the proportion of patients who reported being “very much improved” or “much improved” over baseline (P = .0580), Biogen reported.

In addition, a numeric advantage of 350 mg over placebo was observed in the proportion of patients with a 2-point or greater improvement in ADP score and the proportion with at least a 30% reduction in ADP at 12 weeks, but these also did not reach statistical significance.

Both doses of vixotrigine were “generally well tolerated and the safety profile was consistent with previous studies of vixotrigine with no evidence of abuse potential,” the company said.

In the open-label period, common adverse events seen in at least 2.5% of patients were dizziness, headache, vertigo, and nausea; adverse events led 5.3% of patients to discontinue the open-label portion of the study. Across the entire study, most adverse events were mild or moderate in severity.

“The totality of data from the vixotrigine program will inform potential doses for study in future phase 3 clinical trials,” the company said.

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

Top-line results from a phase 2 study suggest vixotrigine (BIIB074, Biogen), a nonopioid investigational oral pain medication, reduces chronic neuropathic pain caused by small fiber neuropathy (SFN) and is generally well tolerated.

“We are encouraged by the overall results of the CONVEY study, especially given the significant unmet medical need for additional agents to treat chronic painful neuropathy,” Katherine Dawson, MD, senior vice president and head of the therapeutics development unit at Biogen, said in a news release.

Vixotrigine (BIIB074) is a peripherally and centrally acting, orally administered, voltage- and use-dependent voltage-gated sodium channel blocker.

CONVEY was a phase 2, placebo-controlled, double-blind, randomized withdrawal study of 265 patients experiencing pain from confirmed idiopathic or diabetes-associated SFN.

Following a 4-week open-label run-in period, 123 responders to vixotrigine were randomly allocated to 200 mg or 350 mg vixotrigine or placebo twice daily for 12 weeks in the double-blind portion of the study.

At week 12, vixotrigine 200 mg twice daily met the primary endpoint of a statistically significant reduction from baseline in the mean average daily pain (ADP) score versus placebo (P = .0501).

A subgroup analysis showed a treatment effect in patients with diabetes-associated SFN but not in the smaller subgroup of patients with idiopathic SFN.

The 200-mg dose also led to a significant improvement over placebo in mean worst daily pain score at 12 weeks (P = .0455).

A numeric advantage of 200 mg vixotrigine over placebo was observed in additional secondary endpoints, including the proportion of patients with at least a 2-point improvement in ADP score and the proportion with at least a 30% reduction in ADP at week 12, but these failed to reach statistical significance.

Vixotrigine 350 mg twice daily did not meet the primary endpoint of mean change in ADP at 12 weeks.

However, treatment at the higher dose led to a significant increase in the proportion of patients who reported being “very much improved” or “much improved” over baseline (P = .0580), Biogen reported.

In addition, a numeric advantage of 350 mg over placebo was observed in the proportion of patients with a 2-point or greater improvement in ADP score and the proportion with at least a 30% reduction in ADP at 12 weeks, but these also did not reach statistical significance.

Both doses of vixotrigine were “generally well tolerated and the safety profile was consistent with previous studies of vixotrigine with no evidence of abuse potential,” the company said.

In the open-label period, common adverse events seen in at least 2.5% of patients were dizziness, headache, vertigo, and nausea; adverse events led 5.3% of patients to discontinue the open-label portion of the study. Across the entire study, most adverse events were mild or moderate in severity.

“The totality of data from the vixotrigine program will inform potential doses for study in future phase 3 clinical trials,” the company said.

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

Top-line results from a phase 2 study suggest vixotrigine (BIIB074, Biogen), a nonopioid investigational oral pain medication, reduces chronic neuropathic pain caused by small fiber neuropathy (SFN) and is generally well tolerated.

“We are encouraged by the overall results of the CONVEY study, especially given the significant unmet medical need for additional agents to treat chronic painful neuropathy,” Katherine Dawson, MD, senior vice president and head of the therapeutics development unit at Biogen, said in a news release.

Vixotrigine (BIIB074) is a peripherally and centrally acting, orally administered, voltage- and use-dependent voltage-gated sodium channel blocker.

CONVEY was a phase 2, placebo-controlled, double-blind, randomized withdrawal study of 265 patients experiencing pain from confirmed idiopathic or diabetes-associated SFN.

Following a 4-week open-label run-in period, 123 responders to vixotrigine were randomly allocated to 200 mg or 350 mg vixotrigine or placebo twice daily for 12 weeks in the double-blind portion of the study.

At week 12, vixotrigine 200 mg twice daily met the primary endpoint of a statistically significant reduction from baseline in the mean average daily pain (ADP) score versus placebo (P = .0501).

A subgroup analysis showed a treatment effect in patients with diabetes-associated SFN but not in the smaller subgroup of patients with idiopathic SFN.

The 200-mg dose also led to a significant improvement over placebo in mean worst daily pain score at 12 weeks (P = .0455).

A numeric advantage of 200 mg vixotrigine over placebo was observed in additional secondary endpoints, including the proportion of patients with at least a 2-point improvement in ADP score and the proportion with at least a 30% reduction in ADP at week 12, but these failed to reach statistical significance.

Vixotrigine 350 mg twice daily did not meet the primary endpoint of mean change in ADP at 12 weeks.

However, treatment at the higher dose led to a significant increase in the proportion of patients who reported being “very much improved” or “much improved” over baseline (P = .0580), Biogen reported.

In addition, a numeric advantage of 350 mg over placebo was observed in the proportion of patients with a 2-point or greater improvement in ADP score and the proportion with at least a 30% reduction in ADP at 12 weeks, but these also did not reach statistical significance.

Both doses of vixotrigine were “generally well tolerated and the safety profile was consistent with previous studies of vixotrigine with no evidence of abuse potential,” the company said.

In the open-label period, common adverse events seen in at least 2.5% of patients were dizziness, headache, vertigo, and nausea; adverse events led 5.3% of patients to discontinue the open-label portion of the study. Across the entire study, most adverse events were mild or moderate in severity.

“The totality of data from the vixotrigine program will inform potential doses for study in future phase 3 clinical trials,” the company said.

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

Patients with chronic lymphocytic leukemia have similar outcomes following cardiac operations as patients without CLL, but commonly require more blood transfusions, according to the results of retrospective cohort study using the 2010-2017 Nationwide Readmissions Database (NRD).

The researchers assessed all adult patients undergoing elective coronary artery bypass grafting, valve repair, or valve replacement as identified using the NRD.

Patients were stratified by history of CLL and the incidence of in-hospital mortality, perioperative complications, blood transfusions, and readmission within 90 days were examined. A 3:1 nearest-neighbor matching was performed between patients with and without CLL for all primary and secondary outcomes of interest, according to the report, published online in Annals of Thoracic Surgery.
 

Comparable results

A total of 1,250,882 patients in the database were found who underwent cardiac operations. Of these, 0.23% had a diagnosis of CLL. Among 11,237 propensity-matched patients, those with CLL had similar rates of in-hospital mortality (3.8% vs. 2.6%, P = .08) and perioperative complications (33.4% vs. 33.6%, P = .92), compared with their non-CLL counterparts. However, the incidence of infection was comparable (8.5% vs. 9.4%, P = .38).

However, patients with CLL required blood transfusions more frequently (33.7% vs. 28.4%, P = .003) than did patients without CLL. In addition, patients with CLL were more likely to be readmitted within 90 days of discharge, compared with their counterparts, and “respiratory reasons, including pneumonia, contributed significantly to the readmission burden in this cohort,” the researchers, led by Josef Madrigal, BS, of the University of California, Los Angeles, stated.

“The inherent risk of transfusion and the possible benefits of blood conservation interventions must be considered in this patient population. Increased risk of rehospitalization in patients with CLL suggests the need for measures aimed at mitigating the risk of respiratory complications,” the researchers concluded.

There were no conflicts of interest reported in the article.

[email protected]

Patients with chronic lymphocytic leukemia have similar outcomes following cardiac operations as patients without CLL, but commonly require more blood transfusions, according to the results of retrospective cohort study using the 2010-2017 Nationwide Readmissions Database (NRD).

The researchers assessed all adult patients undergoing elective coronary artery bypass grafting, valve repair, or valve replacement as identified using the NRD.

Patients were stratified by history of CLL and the incidence of in-hospital mortality, perioperative complications, blood transfusions, and readmission within 90 days were examined. A 3:1 nearest-neighbor matching was performed between patients with and without CLL for all primary and secondary outcomes of interest, according to the report, published online in Annals of Thoracic Surgery.
 

Comparable results

A total of 1,250,882 patients in the database were found who underwent cardiac operations. Of these, 0.23% had a diagnosis of CLL. Among 11,237 propensity-matched patients, those with CLL had similar rates of in-hospital mortality (3.8% vs. 2.6%, P = .08) and perioperative complications (33.4% vs. 33.6%, P = .92), compared with their non-CLL counterparts. However, the incidence of infection was comparable (8.5% vs. 9.4%, P = .38).

However, patients with CLL required blood transfusions more frequently (33.7% vs. 28.4%, P = .003) than did patients without CLL. In addition, patients with CLL were more likely to be readmitted within 90 days of discharge, compared with their counterparts, and “respiratory reasons, including pneumonia, contributed significantly to the readmission burden in this cohort,” the researchers, led by Josef Madrigal, BS, of the University of California, Los Angeles, stated.

“The inherent risk of transfusion and the possible benefits of blood conservation interventions must be considered in this patient population. Increased risk of rehospitalization in patients with CLL suggests the need for measures aimed at mitigating the risk of respiratory complications,” the researchers concluded.

There were no conflicts of interest reported in the article.

[email protected]

Patients with chronic lymphocytic leukemia have similar outcomes following cardiac operations as patients without CLL, but commonly require more blood transfusions, according to the results of retrospective cohort study using the 2010-2017 Nationwide Readmissions Database (NRD).

The researchers assessed all adult patients undergoing elective coronary artery bypass grafting, valve repair, or valve replacement as identified using the NRD.

Patients were stratified by history of CLL and the incidence of in-hospital mortality, perioperative complications, blood transfusions, and readmission within 90 days were examined. A 3:1 nearest-neighbor matching was performed between patients with and without CLL for all primary and secondary outcomes of interest, according to the report, published online in Annals of Thoracic Surgery.
 

Comparable results

A total of 1,250,882 patients in the database were found who underwent cardiac operations. Of these, 0.23% had a diagnosis of CLL. Among 11,237 propensity-matched patients, those with CLL had similar rates of in-hospital mortality (3.8% vs. 2.6%, P = .08) and perioperative complications (33.4% vs. 33.6%, P = .92), compared with their non-CLL counterparts. However, the incidence of infection was comparable (8.5% vs. 9.4%, P = .38).

However, patients with CLL required blood transfusions more frequently (33.7% vs. 28.4%, P = .003) than did patients without CLL. In addition, patients with CLL were more likely to be readmitted within 90 days of discharge, compared with their counterparts, and “respiratory reasons, including pneumonia, contributed significantly to the readmission burden in this cohort,” the researchers, led by Josef Madrigal, BS, of the University of California, Los Angeles, stated.

“The inherent risk of transfusion and the possible benefits of blood conservation interventions must be considered in this patient population. Increased risk of rehospitalization in patients with CLL suggests the need for measures aimed at mitigating the risk of respiratory complications,” the researchers concluded.

There were no conflicts of interest reported in the article.

[email protected]

Progression free survival was significantly better in unresectable stage 3 non–small cell lung cancer when patients were treated with durvalumab in combination with other immunotherapies, instead of durvalumab alone, following chemoradiotherapy.

Both combinations – durvalumab plus either the anti-CD73 monoclonal antibody oleclumab or the anti-NKG2A mAb monalizumab – also numerically improved objective response rate. “Safety profiles were consistent across arms and no new safety signals were identified,” said Alexandre Martinez-Marti, MD, the lead investigator on the phase 2 trial, dubbed COAST, which he presented (abstract LBA42) at the 2021 European Society for Medical Oncology Congress on Sept. 17.

“These data support further evaluations of these combinations,” said Dr. Martinez-Marti, also a thoracic medical oncologist at the Vall d’Hebron Institute of Oncology in Barcelona.

Durvalumab is already established as a standard of care option for patients with unresectable stage 3 NSCLC who don’t progress after concurrent chemoradiation. There’s been preliminary data suggesting the benefits might be greater with oleclumab or monalizumab, so the study team looked into the issue.

They randomized 66 patients with unresectable stage 3 NSCLC and no progression after chemoradiotherapy to durvalumab 1,500 mg IV every 4 weeks; 59 others to durvalumab at the same dosage plus oleclumab 3,000 mg IV every 2 weeks for the first two cycles then every 4 weeks, and 61 were randomized to durvalumab plus monalizumab 750 mg IV every 2 weeks.

Patients were treated for up to 12 months, and they started treatment no later than 42 days after completing chemoradiation.

Over a median follow-up of 11.5 months, median progression-free survival (PFS) was 6.3 months in the durvalumab arm, but 15.1 months with the monalizumab combination (PFS hazard ratio versus durvalumab alone, 0.65; 95% CI, 0.49-0.85), and not reached in the oleclumab arm (PFS HR, 0.44; 95% CI, 0.26-0.75).

There were only a few complete responders across the study groups. Partial responses rates were 22.4% of the durvalumab alone arm, 36.7% in the oleclumab group, and 32.3% in the monalizumab arm.

The investigator assessed objective response rate was 25.4% with durvalumab alone, 38.3% in the oleclumab group, and 37.1% with the monalizumab combination. Curves started to separate from durvalumab monotherapy at around 2-4 months.

“Overall, the safety profiles of the two combinations were generally similar to the safety profile of durvalumab alone,” Dr. Martinez-Marti said. The rate of grade 3 or higher treatment-emergent events incidence was 39.4% with durvalumab, 40.7% the oleclumab combination, and 27.9% with monalizumab.

The most common grade 3/4 events were pneumonia (5.9%) and decreased lymphocyte count (3.2%); both were less common with the monalizumab combination.

Combined rates of pneumonitis and radiation pneumonitis of any grade were 21.2% with durvalumab, 28.8% in the oleclumab group, and 21.3% with monalizumab.

The groups were generally well balanced at baseline. The majority of subjects were men, White, and former smokers. Most subjects had stage 3A or 3B disease.

The work was funded by AstraZeneca. The investigators disclosed numerous ties to the company, including Dr. Martinez-Marti, who reported personal fees, travel expenses, and other connections.

This article was updated 9/24/21.

[email protected]

Progression free survival was significantly better in unresectable stage 3 non–small cell lung cancer when patients were treated with durvalumab in combination with other immunotherapies, instead of durvalumab alone, following chemoradiotherapy.

Both combinations – durvalumab plus either the anti-CD73 monoclonal antibody oleclumab or the anti-NKG2A mAb monalizumab – also numerically improved objective response rate. “Safety profiles were consistent across arms and no new safety signals were identified,” said Alexandre Martinez-Marti, MD, the lead investigator on the phase 2 trial, dubbed COAST, which he presented (abstract LBA42) at the 2021 European Society for Medical Oncology Congress on Sept. 17.

“These data support further evaluations of these combinations,” said Dr. Martinez-Marti, also a thoracic medical oncologist at the Vall d’Hebron Institute of Oncology in Barcelona.

Durvalumab is already established as a standard of care option for patients with unresectable stage 3 NSCLC who don’t progress after concurrent chemoradiation. There’s been preliminary data suggesting the benefits might be greater with oleclumab or monalizumab, so the study team looked into the issue.

They randomized 66 patients with unresectable stage 3 NSCLC and no progression after chemoradiotherapy to durvalumab 1,500 mg IV every 4 weeks; 59 others to durvalumab at the same dosage plus oleclumab 3,000 mg IV every 2 weeks for the first two cycles then every 4 weeks, and 61 were randomized to durvalumab plus monalizumab 750 mg IV every 2 weeks.

Patients were treated for up to 12 months, and they started treatment no later than 42 days after completing chemoradiation.

Over a median follow-up of 11.5 months, median progression-free survival (PFS) was 6.3 months in the durvalumab arm, but 15.1 months with the monalizumab combination (PFS hazard ratio versus durvalumab alone, 0.65; 95% CI, 0.49-0.85), and not reached in the oleclumab arm (PFS HR, 0.44; 95% CI, 0.26-0.75).

There were only a few complete responders across the study groups. Partial responses rates were 22.4% of the durvalumab alone arm, 36.7% in the oleclumab group, and 32.3% in the monalizumab arm.

The investigator assessed objective response rate was 25.4% with durvalumab alone, 38.3% in the oleclumab group, and 37.1% with the monalizumab combination. Curves started to separate from durvalumab monotherapy at around 2-4 months.

“Overall, the safety profiles of the two combinations were generally similar to the safety profile of durvalumab alone,” Dr. Martinez-Marti said. The rate of grade 3 or higher treatment-emergent events incidence was 39.4% with durvalumab, 40.7% the oleclumab combination, and 27.9% with monalizumab.

The most common grade 3/4 events were pneumonia (5.9%) and decreased lymphocyte count (3.2%); both were less common with the monalizumab combination.

Combined rates of pneumonitis and radiation pneumonitis of any grade were 21.2% with durvalumab, 28.8% in the oleclumab group, and 21.3% with monalizumab.

The groups were generally well balanced at baseline. The majority of subjects were men, White, and former smokers. Most subjects had stage 3A or 3B disease.

The work was funded by AstraZeneca. The investigators disclosed numerous ties to the company, including Dr. Martinez-Marti, who reported personal fees, travel expenses, and other connections.

This article was updated 9/24/21.

[email protected]

Progression free survival was significantly better in unresectable stage 3 non–small cell lung cancer when patients were treated with durvalumab in combination with other immunotherapies, instead of durvalumab alone, following chemoradiotherapy.

Both combinations – durvalumab plus either the anti-CD73 monoclonal antibody oleclumab or the anti-NKG2A mAb monalizumab – also numerically improved objective response rate. “Safety profiles were consistent across arms and no new safety signals were identified,” said Alexandre Martinez-Marti, MD, the lead investigator on the phase 2 trial, dubbed COAST, which he presented (abstract LBA42) at the 2021 European Society for Medical Oncology Congress on Sept. 17.

“These data support further evaluations of these combinations,” said Dr. Martinez-Marti, also a thoracic medical oncologist at the Vall d’Hebron Institute of Oncology in Barcelona.

Durvalumab is already established as a standard of care option for patients with unresectable stage 3 NSCLC who don’t progress after concurrent chemoradiation. There’s been preliminary data suggesting the benefits might be greater with oleclumab or monalizumab, so the study team looked into the issue.

They randomized 66 patients with unresectable stage 3 NSCLC and no progression after chemoradiotherapy to durvalumab 1,500 mg IV every 4 weeks; 59 others to durvalumab at the same dosage plus oleclumab 3,000 mg IV every 2 weeks for the first two cycles then every 4 weeks, and 61 were randomized to durvalumab plus monalizumab 750 mg IV every 2 weeks.

Patients were treated for up to 12 months, and they started treatment no later than 42 days after completing chemoradiation.

Over a median follow-up of 11.5 months, median progression-free survival (PFS) was 6.3 months in the durvalumab arm, but 15.1 months with the monalizumab combination (PFS hazard ratio versus durvalumab alone, 0.65; 95% CI, 0.49-0.85), and not reached in the oleclumab arm (PFS HR, 0.44; 95% CI, 0.26-0.75).

There were only a few complete responders across the study groups. Partial responses rates were 22.4% of the durvalumab alone arm, 36.7% in the oleclumab group, and 32.3% in the monalizumab arm.

The investigator assessed objective response rate was 25.4% with durvalumab alone, 38.3% in the oleclumab group, and 37.1% with the monalizumab combination. Curves started to separate from durvalumab monotherapy at around 2-4 months.

“Overall, the safety profiles of the two combinations were generally similar to the safety profile of durvalumab alone,” Dr. Martinez-Marti said. The rate of grade 3 or higher treatment-emergent events incidence was 39.4% with durvalumab, 40.7% the oleclumab combination, and 27.9% with monalizumab.

The most common grade 3/4 events were pneumonia (5.9%) and decreased lymphocyte count (3.2%); both were less common with the monalizumab combination.

Combined rates of pneumonitis and radiation pneumonitis of any grade were 21.2% with durvalumab, 28.8% in the oleclumab group, and 21.3% with monalizumab.

The groups were generally well balanced at baseline. The majority of subjects were men, White, and former smokers. Most subjects had stage 3A or 3B disease.

The work was funded by AstraZeneca. The investigators disclosed numerous ties to the company, including Dr. Martinez-Marti, who reported personal fees, travel expenses, and other connections.

This article was updated 9/24/21.

[email protected]

While postoperative conformal radiotherapy (PORT) reduces the risk of mediastinal relapse in completely resected non–small cell lung cancer with mediastinal nodal metastases (N2), it does not have a significant impact on disease-free and overall survival, according to a report (abstract 1170O) recently presented at the 2021 European Society for Medical Oncology Congress on Sept. 17.

The report was an update on the LungART international clinical trial, which, at the 2020 ESMO meeting, was shown not to improve disease-free survival over the course of 3 years. The update showed that, in addition to the lack of disease-free survival benefit, there was also no difference in metastases, and patients randomized to PORT had higher rates of death and grade 3/4 cardiopulmonary toxicity. The investigators returned this year to expand on another finding from the trial, a 51% reduction in the risk of mediastinal relapse with postoperative radiotherapy. The new analysis suggests there might still be a role for PORT in select patients, perhaps those with heavy nodal involvement, said lead investigator and presenter Cecile Le Pechoux, MD, radiation oncologist at the Gustave Roussy cancer treatment center in Villejuif, France.

For now, “personalized prescription of PORT should be based on prognostic factors of relapse and joint assessment of toxicity and efficacy,” she said.

Study discussant Pilar Garrido, MD, PhD, head of thoracic tumors Ramon y Cajal University Hospital, Madrid, agreed that there might still be a benefit for people with multiple N2 nodal station involvement, but at present, she said, “for me PORT cannot be the standard of care ... given the toxicity and mortality among PORT patients in LungART.”

The trial randomized 501 patients with non–small cell lung cancer with mediastinal involvement to either PORT at 54 Gy over 5.5 weeks or no further treatment following complete resection. Neoadjuvant or adjuvant chemotherapy were allowed.

The 3-year mediastinal relapse-free survival was 72.26% in the control arm but 86.06% with PORT (hazard ratio, 0.45; 95% confidence interval, 0.3-0.69).

“There is a significant difference” when it comes to mediastinal relapse, and “patients who have PORT do better. If we look at the location of mediastinal relapse, most [patients] relapse within the initially involved node. This is important information,” Dr. Le Pechoux said.

For left-sided tumors, the most frequent sites of mediastinal relapse were thoracic lymph node stations 7, 4L, and 4R. For right sided tumors, the most frequent stations were 4R, 2R and 7.

Prognostic factors for disease-free survival included quality of resection, extent of mediastinal involvement, and lymph node ratio (involved/explored). Nodal involvement was a significant prognostic factor for overall survival, but PORT was not (HR, 0.98; 95% CI, 0.7-1.4).

Mediastinal involvement with more than two node stations and less than an RO, or microscopically margin-negative resection, increased the risk of relapse.

The work was funded by the French National Cancer Institute, French Health Ministry, Institute Gustave Roussy, and Cancer Research UK. Dr. Pechoux and Dr. Garido disclosed ties to AstraZeneca, Roche, Amgen, and other companies.

This article was updated 9/24/21.

[email protected]

While postoperative conformal radiotherapy (PORT) reduces the risk of mediastinal relapse in completely resected non–small cell lung cancer with mediastinal nodal metastases (N2), it does not have a significant impact on disease-free and overall survival, according to a report (abstract 1170O) recently presented at the 2021 European Society for Medical Oncology Congress on Sept. 17.

The report was an update on the LungART international clinical trial, which, at the 2020 ESMO meeting, was shown not to improve disease-free survival over the course of 3 years. The update showed that, in addition to the lack of disease-free survival benefit, there was also no difference in metastases, and patients randomized to PORT had higher rates of death and grade 3/4 cardiopulmonary toxicity. The investigators returned this year to expand on another finding from the trial, a 51% reduction in the risk of mediastinal relapse with postoperative radiotherapy. The new analysis suggests there might still be a role for PORT in select patients, perhaps those with heavy nodal involvement, said lead investigator and presenter Cecile Le Pechoux, MD, radiation oncologist at the Gustave Roussy cancer treatment center in Villejuif, France.

For now, “personalized prescription of PORT should be based on prognostic factors of relapse and joint assessment of toxicity and efficacy,” she said.

Study discussant Pilar Garrido, MD, PhD, head of thoracic tumors Ramon y Cajal University Hospital, Madrid, agreed that there might still be a benefit for people with multiple N2 nodal station involvement, but at present, she said, “for me PORT cannot be the standard of care ... given the toxicity and mortality among PORT patients in LungART.”

The trial randomized 501 patients with non–small cell lung cancer with mediastinal involvement to either PORT at 54 Gy over 5.5 weeks or no further treatment following complete resection. Neoadjuvant or adjuvant chemotherapy were allowed.

The 3-year mediastinal relapse-free survival was 72.26% in the control arm but 86.06% with PORT (hazard ratio, 0.45; 95% confidence interval, 0.3-0.69).

“There is a significant difference” when it comes to mediastinal relapse, and “patients who have PORT do better. If we look at the location of mediastinal relapse, most [patients] relapse within the initially involved node. This is important information,” Dr. Le Pechoux said.

For left-sided tumors, the most frequent sites of mediastinal relapse were thoracic lymph node stations 7, 4L, and 4R. For right sided tumors, the most frequent stations were 4R, 2R and 7.

Prognostic factors for disease-free survival included quality of resection, extent of mediastinal involvement, and lymph node ratio (involved/explored). Nodal involvement was a significant prognostic factor for overall survival, but PORT was not (HR, 0.98; 95% CI, 0.7-1.4).

Mediastinal involvement with more than two node stations and less than an RO, or microscopically margin-negative resection, increased the risk of relapse.

The work was funded by the French National Cancer Institute, French Health Ministry, Institute Gustave Roussy, and Cancer Research UK. Dr. Pechoux and Dr. Garido disclosed ties to AstraZeneca, Roche, Amgen, and other companies.

This article was updated 9/24/21.

[email protected]

While postoperative conformal radiotherapy (PORT) reduces the risk of mediastinal relapse in completely resected non–small cell lung cancer with mediastinal nodal metastases (N2), it does not have a significant impact on disease-free and overall survival, according to a report (abstract 1170O) recently presented at the 2021 European Society for Medical Oncology Congress on Sept. 17.

The report was an update on the LungART international clinical trial, which, at the 2020 ESMO meeting, was shown not to improve disease-free survival over the course of 3 years. The update showed that, in addition to the lack of disease-free survival benefit, there was also no difference in metastases, and patients randomized to PORT had higher rates of death and grade 3/4 cardiopulmonary toxicity. The investigators returned this year to expand on another finding from the trial, a 51% reduction in the risk of mediastinal relapse with postoperative radiotherapy. The new analysis suggests there might still be a role for PORT in select patients, perhaps those with heavy nodal involvement, said lead investigator and presenter Cecile Le Pechoux, MD, radiation oncologist at the Gustave Roussy cancer treatment center in Villejuif, France.

For now, “personalized prescription of PORT should be based on prognostic factors of relapse and joint assessment of toxicity and efficacy,” she said.

Study discussant Pilar Garrido, MD, PhD, head of thoracic tumors Ramon y Cajal University Hospital, Madrid, agreed that there might still be a benefit for people with multiple N2 nodal station involvement, but at present, she said, “for me PORT cannot be the standard of care ... given the toxicity and mortality among PORT patients in LungART.”

The trial randomized 501 patients with non–small cell lung cancer with mediastinal involvement to either PORT at 54 Gy over 5.5 weeks or no further treatment following complete resection. Neoadjuvant or adjuvant chemotherapy were allowed.

The 3-year mediastinal relapse-free survival was 72.26% in the control arm but 86.06% with PORT (hazard ratio, 0.45; 95% confidence interval, 0.3-0.69).

“There is a significant difference” when it comes to mediastinal relapse, and “patients who have PORT do better. If we look at the location of mediastinal relapse, most [patients] relapse within the initially involved node. This is important information,” Dr. Le Pechoux said.

For left-sided tumors, the most frequent sites of mediastinal relapse were thoracic lymph node stations 7, 4L, and 4R. For right sided tumors, the most frequent stations were 4R, 2R and 7.

Prognostic factors for disease-free survival included quality of resection, extent of mediastinal involvement, and lymph node ratio (involved/explored). Nodal involvement was a significant prognostic factor for overall survival, but PORT was not (HR, 0.98; 95% CI, 0.7-1.4).

Mediastinal involvement with more than two node stations and less than an RO, or microscopically margin-negative resection, increased the risk of relapse.

The work was funded by the French National Cancer Institute, French Health Ministry, Institute Gustave Roussy, and Cancer Research UK. Dr. Pechoux and Dr. Garido disclosed ties to AstraZeneca, Roche, Amgen, and other companies.

This article was updated 9/24/21.

[email protected]

The new standard of care for women with persistent, recurrent, or perhaps primary metastatic cervical cancer should be pembrolizumab added to chemotherapy with bevacizumab in [the] biomarker-positive population.

That declaration was made by Raza Mirza, MD, chief oncologist at Copenhagen University Hospital in Denmark, who was invited to discuss the pros and cons of the KEYNOTE-826 trial at the European Society for Medical Oncology (ESMO) Congress 2021.

The trial showed that adding the checkpoint inhibitor pembrolizumab (Keytruda) to standard chemotherapy — with or without bevacizumab — resulted in about a one third reduction in the risk for both disease progression and death compared with chemotherapy alone.

The benefit of adding pembrolizumab was seen both in the overall study population and in patients with higher levels of programmed death ligand-1 (PD-L1), but not in those with biomarker-negative tumors, reported investigator Nicoletta Colombo, MD, PhD, from the University of Milan-Bicocca, Italy.

“Overall, data from KEYNOTE-826 suggest that pembrolizumab plus platinum-based chemotherapy with or without bevacizumab may be a new first-line standard of care,” she said in a late-breaking oral abstract presentation. The study was also simultaneously published online in The New England Journal of Medicine.

Since 2014, the standard of care for treating patients with recurrent, persistent, or metastatic cervical cancer has been chemotherapy with a platinum compound, paclitaxel, plus bevacizumab, based on the results of the GOG 240 study.

Immunotherapy with PD-1 inhibitors have shown efficacy as monotherapy in second- or later-line therapy for women with cervical cancer, but until now no data about the addition of these agents to chemotherapy were available, Dr. Colombo noted.

Dr. Mirza noted that there is sound rationale for using checkpoint inhibitors targeted against PD-1 in patients with cervical cancer, because PD-L1 has been shown to be a consistent biomarker for infection of the cervix with human papillomavirus (HPV), which is responsible for more than 90% of cervical cancers.

“PD-L1 is significantly upregulated in cervical cancer and detectable by immunohistochemistry,” he said. “PD-L1 expression reduces the immune response since it is able to bind to PD-1 on T-cell lymphocytes, thereby inhibiting their function. These findings suggest that targeting the PD-1/PD-L1 pathway may be therapeutically effective and should be considered in the treatment of cervical cancer.”

KEYNOTE-826 details

This was a double-blind trial conducted in 617 patients stratified by metastatic disease status at diagnosis; PD-L1 combined positive score (CPS) either < 1, 1 to < 10, or ≥ 10. They were randomized in a 1:1 ratio to receive pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy, with bevacizumab added at the investigator’s discretion.

The dual primary endpoints of progression-free survival (PFS) and overall survival (OS) were each tested sequentially in patients with a PD-L1 CPS ≥ 1 in both the intention-to-treat (ITT) or “all-comers” population, and in patients with a PD-L1 CPS ≥ 10.

Patient characteristics were generally well balanced between the treatment groups, except for a slightly higher proportion of patients with squamous cell histology in the pembrolizumab versus the placebo group (76.3% vs 68.3%).

PFS and OS results

The addition of pembrolizumab was associated with improved PFS across most protocol-specified subgroups, Dr. Colombo and colleagues noted.

After a median follow-up of 22 months, the 12-month PFS rate in the biomarker-selected population (all patients with a PD-L1 CPS ≥ 1) was 45.5% for patients in the pembrolizumab group versus 34.1% in the placebo group. This translated into a hazard ratio (HR) for progression on pembrolizumab of 0.62 (P < .001).

The respective PFS rates in the ITT population were 44.7% and 33.5%, with an HR for progression of 0.65 (P < .001) with the checkpoint inhibitor.

In patients with PD-L1 CPS ≥ 10, the respective rates of PFS and the HR were 44.6%, 33.5%, and 0.58 (P < .001).

OS rates were also significantly improved, he noted.

The 12-month and 24-month OS rates in all patients with PD-L1 CPS ≥ 1 were 75.3% and 53%, respectively, for patients assigned to pembrolizumab versus 63.1% and 41.7% in patients assigned to placebo, translating to an HR for death with pembrolizumab in this group of 0.64 (P < .001).

In the all-comers (ITT) population, respective 12- and 24-month OS rates were 74.8% and 50.4% with pembrolizumab versus 63.6% and 40.4% with placebo. This difference translated into an HR for death with anti-PD-1 of 0.67 (P < .001).

Among patients with the higher PD-L1 levels (≥ CPS 10), the respective OS rates were 75.7% and 54.4% with pembrolizumab versus 61.5% and 44.6% with placebo (HR 0.61, P < .001).

Dr. Mirza emphasized that “we did not see any efficacy of pembrolizumab in the biomarker-negative population,” with an HR for PFS of 0.94 and HR for OS of 1.0 in this subgroup.

The most common grade ≥ 3 adverse events were anemia, which occurred in 30.3% of patients assigned to pembrolizumab compared with 26.9% in the placebo group, and neutropenias, which occurred in 12.4% and 9.7% of patients, respectively. One patient in the pembrolizumab group died from an immune-related event, encephalitis.

Despite his enthusiasm for the regimen, Dr. Mirza tempered it by pointing out that there was an imbalance in the sample sizes regarding histology, and a potential bias introduced by the failure to stratify by tumor histology.

He noted that in other studies checkpoint inhibitors have had only modest activity against adenocarcinomas, which were more frequent in the placebo group in KEYNOTE-826, resulting in a potential positive bias in favor of pembrolizumab.

KEYNOTE-826 is funded by MSD. Dr. Colombo has disclosed consultant, research, and promotional speaking activities for multiple companies. Dr. Mirza has disclosed personal financial interests with Merck and other companies.


A version of this article was first published on Medscape.com.

The new standard of care for women with persistent, recurrent, or perhaps primary metastatic cervical cancer should be pembrolizumab added to chemotherapy with bevacizumab in [the] biomarker-positive population.

That declaration was made by Raza Mirza, MD, chief oncologist at Copenhagen University Hospital in Denmark, who was invited to discuss the pros and cons of the KEYNOTE-826 trial at the European Society for Medical Oncology (ESMO) Congress 2021.

The trial showed that adding the checkpoint inhibitor pembrolizumab (Keytruda) to standard chemotherapy — with or without bevacizumab — resulted in about a one third reduction in the risk for both disease progression and death compared with chemotherapy alone.

The benefit of adding pembrolizumab was seen both in the overall study population and in patients with higher levels of programmed death ligand-1 (PD-L1), but not in those with biomarker-negative tumors, reported investigator Nicoletta Colombo, MD, PhD, from the University of Milan-Bicocca, Italy.

“Overall, data from KEYNOTE-826 suggest that pembrolizumab plus platinum-based chemotherapy with or without bevacizumab may be a new first-line standard of care,” she said in a late-breaking oral abstract presentation. The study was also simultaneously published online in The New England Journal of Medicine.

Since 2014, the standard of care for treating patients with recurrent, persistent, or metastatic cervical cancer has been chemotherapy with a platinum compound, paclitaxel, plus bevacizumab, based on the results of the GOG 240 study.

Immunotherapy with PD-1 inhibitors have shown efficacy as monotherapy in second- or later-line therapy for women with cervical cancer, but until now no data about the addition of these agents to chemotherapy were available, Dr. Colombo noted.

Dr. Mirza noted that there is sound rationale for using checkpoint inhibitors targeted against PD-1 in patients with cervical cancer, because PD-L1 has been shown to be a consistent biomarker for infection of the cervix with human papillomavirus (HPV), which is responsible for more than 90% of cervical cancers.

“PD-L1 is significantly upregulated in cervical cancer and detectable by immunohistochemistry,” he said. “PD-L1 expression reduces the immune response since it is able to bind to PD-1 on T-cell lymphocytes, thereby inhibiting their function. These findings suggest that targeting the PD-1/PD-L1 pathway may be therapeutically effective and should be considered in the treatment of cervical cancer.”

KEYNOTE-826 details

This was a double-blind trial conducted in 617 patients stratified by metastatic disease status at diagnosis; PD-L1 combined positive score (CPS) either < 1, 1 to < 10, or ≥ 10. They were randomized in a 1:1 ratio to receive pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy, with bevacizumab added at the investigator’s discretion.

The dual primary endpoints of progression-free survival (PFS) and overall survival (OS) were each tested sequentially in patients with a PD-L1 CPS ≥ 1 in both the intention-to-treat (ITT) or “all-comers” population, and in patients with a PD-L1 CPS ≥ 10.

Patient characteristics were generally well balanced between the treatment groups, except for a slightly higher proportion of patients with squamous cell histology in the pembrolizumab versus the placebo group (76.3% vs 68.3%).

PFS and OS results

The addition of pembrolizumab was associated with improved PFS across most protocol-specified subgroups, Dr. Colombo and colleagues noted.

After a median follow-up of 22 months, the 12-month PFS rate in the biomarker-selected population (all patients with a PD-L1 CPS ≥ 1) was 45.5% for patients in the pembrolizumab group versus 34.1% in the placebo group. This translated into a hazard ratio (HR) for progression on pembrolizumab of 0.62 (P < .001).

The respective PFS rates in the ITT population were 44.7% and 33.5%, with an HR for progression of 0.65 (P < .001) with the checkpoint inhibitor.

In patients with PD-L1 CPS ≥ 10, the respective rates of PFS and the HR were 44.6%, 33.5%, and 0.58 (P < .001).

OS rates were also significantly improved, he noted.

The 12-month and 24-month OS rates in all patients with PD-L1 CPS ≥ 1 were 75.3% and 53%, respectively, for patients assigned to pembrolizumab versus 63.1% and 41.7% in patients assigned to placebo, translating to an HR for death with pembrolizumab in this group of 0.64 (P < .001).

In the all-comers (ITT) population, respective 12- and 24-month OS rates were 74.8% and 50.4% with pembrolizumab versus 63.6% and 40.4% with placebo. This difference translated into an HR for death with anti-PD-1 of 0.67 (P < .001).

Among patients with the higher PD-L1 levels (≥ CPS 10), the respective OS rates were 75.7% and 54.4% with pembrolizumab versus 61.5% and 44.6% with placebo (HR 0.61, P < .001).

Dr. Mirza emphasized that “we did not see any efficacy of pembrolizumab in the biomarker-negative population,” with an HR for PFS of 0.94 and HR for OS of 1.0 in this subgroup.

The most common grade ≥ 3 adverse events were anemia, which occurred in 30.3% of patients assigned to pembrolizumab compared with 26.9% in the placebo group, and neutropenias, which occurred in 12.4% and 9.7% of patients, respectively. One patient in the pembrolizumab group died from an immune-related event, encephalitis.

Despite his enthusiasm for the regimen, Dr. Mirza tempered it by pointing out that there was an imbalance in the sample sizes regarding histology, and a potential bias introduced by the failure to stratify by tumor histology.

He noted that in other studies checkpoint inhibitors have had only modest activity against adenocarcinomas, which were more frequent in the placebo group in KEYNOTE-826, resulting in a potential positive bias in favor of pembrolizumab.

KEYNOTE-826 is funded by MSD. Dr. Colombo has disclosed consultant, research, and promotional speaking activities for multiple companies. Dr. Mirza has disclosed personal financial interests with Merck and other companies.


A version of this article was first published on Medscape.com.

The new standard of care for women with persistent, recurrent, or perhaps primary metastatic cervical cancer should be pembrolizumab added to chemotherapy with bevacizumab in [the] biomarker-positive population.

That declaration was made by Raza Mirza, MD, chief oncologist at Copenhagen University Hospital in Denmark, who was invited to discuss the pros and cons of the KEYNOTE-826 trial at the European Society for Medical Oncology (ESMO) Congress 2021.

The trial showed that adding the checkpoint inhibitor pembrolizumab (Keytruda) to standard chemotherapy — with or without bevacizumab — resulted in about a one third reduction in the risk for both disease progression and death compared with chemotherapy alone.

The benefit of adding pembrolizumab was seen both in the overall study population and in patients with higher levels of programmed death ligand-1 (PD-L1), but not in those with biomarker-negative tumors, reported investigator Nicoletta Colombo, MD, PhD, from the University of Milan-Bicocca, Italy.

“Overall, data from KEYNOTE-826 suggest that pembrolizumab plus platinum-based chemotherapy with or without bevacizumab may be a new first-line standard of care,” she said in a late-breaking oral abstract presentation. The study was also simultaneously published online in The New England Journal of Medicine.

Since 2014, the standard of care for treating patients with recurrent, persistent, or metastatic cervical cancer has been chemotherapy with a platinum compound, paclitaxel, plus bevacizumab, based on the results of the GOG 240 study.

Immunotherapy with PD-1 inhibitors have shown efficacy as monotherapy in second- or later-line therapy for women with cervical cancer, but until now no data about the addition of these agents to chemotherapy were available, Dr. Colombo noted.

Dr. Mirza noted that there is sound rationale for using checkpoint inhibitors targeted against PD-1 in patients with cervical cancer, because PD-L1 has been shown to be a consistent biomarker for infection of the cervix with human papillomavirus (HPV), which is responsible for more than 90% of cervical cancers.

“PD-L1 is significantly upregulated in cervical cancer and detectable by immunohistochemistry,” he said. “PD-L1 expression reduces the immune response since it is able to bind to PD-1 on T-cell lymphocytes, thereby inhibiting their function. These findings suggest that targeting the PD-1/PD-L1 pathway may be therapeutically effective and should be considered in the treatment of cervical cancer.”

KEYNOTE-826 details

This was a double-blind trial conducted in 617 patients stratified by metastatic disease status at diagnosis; PD-L1 combined positive score (CPS) either < 1, 1 to < 10, or ≥ 10. They were randomized in a 1:1 ratio to receive pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy, with bevacizumab added at the investigator’s discretion.

The dual primary endpoints of progression-free survival (PFS) and overall survival (OS) were each tested sequentially in patients with a PD-L1 CPS ≥ 1 in both the intention-to-treat (ITT) or “all-comers” population, and in patients with a PD-L1 CPS ≥ 10.

Patient characteristics were generally well balanced between the treatment groups, except for a slightly higher proportion of patients with squamous cell histology in the pembrolizumab versus the placebo group (76.3% vs 68.3%).

PFS and OS results

The addition of pembrolizumab was associated with improved PFS across most protocol-specified subgroups, Dr. Colombo and colleagues noted.

After a median follow-up of 22 months, the 12-month PFS rate in the biomarker-selected population (all patients with a PD-L1 CPS ≥ 1) was 45.5% for patients in the pembrolizumab group versus 34.1% in the placebo group. This translated into a hazard ratio (HR) for progression on pembrolizumab of 0.62 (P < .001).

The respective PFS rates in the ITT population were 44.7% and 33.5%, with an HR for progression of 0.65 (P < .001) with the checkpoint inhibitor.

In patients with PD-L1 CPS ≥ 10, the respective rates of PFS and the HR were 44.6%, 33.5%, and 0.58 (P < .001).

OS rates were also significantly improved, he noted.

The 12-month and 24-month OS rates in all patients with PD-L1 CPS ≥ 1 were 75.3% and 53%, respectively, for patients assigned to pembrolizumab versus 63.1% and 41.7% in patients assigned to placebo, translating to an HR for death with pembrolizumab in this group of 0.64 (P < .001).

In the all-comers (ITT) population, respective 12- and 24-month OS rates were 74.8% and 50.4% with pembrolizumab versus 63.6% and 40.4% with placebo. This difference translated into an HR for death with anti-PD-1 of 0.67 (P < .001).

Among patients with the higher PD-L1 levels (≥ CPS 10), the respective OS rates were 75.7% and 54.4% with pembrolizumab versus 61.5% and 44.6% with placebo (HR 0.61, P < .001).

Dr. Mirza emphasized that “we did not see any efficacy of pembrolizumab in the biomarker-negative population,” with an HR for PFS of 0.94 and HR for OS of 1.0 in this subgroup.

The most common grade ≥ 3 adverse events were anemia, which occurred in 30.3% of patients assigned to pembrolizumab compared with 26.9% in the placebo group, and neutropenias, which occurred in 12.4% and 9.7% of patients, respectively. One patient in the pembrolizumab group died from an immune-related event, encephalitis.

Despite his enthusiasm for the regimen, Dr. Mirza tempered it by pointing out that there was an imbalance in the sample sizes regarding histology, and a potential bias introduced by the failure to stratify by tumor histology.

He noted that in other studies checkpoint inhibitors have had only modest activity against adenocarcinomas, which were more frequent in the placebo group in KEYNOTE-826, resulting in a potential positive bias in favor of pembrolizumab.

KEYNOTE-826 is funded by MSD. Dr. Colombo has disclosed consultant, research, and promotional speaking activities for multiple companies. Dr. Mirza has disclosed personal financial interests with Merck and other companies.


A version of this article was first published on Medscape.com.

Adjuvant pembrolizumab (Keytruda) following complete melanoma resection could soon move to an earlier stage in the management of high-risk disease, suggest results from KEYNOTE-716. However, the results raise many questions, says an expert invited to discuss the new data.

Adjuvant pembrolizumab is already approved in the United States for use in patients with melanoma with lymph node involvement following complete resection, having been shown to prolong both recurrence-free and distant metastasis-free survival (DMFS) in stage 3 melanoma.

This latest trial involved patients with slightly earlier disease, those with resected stage 2B and 2C melanoma. These patients are at “high risk” of disease recurrence and have similar outcomes to stage 3A and 3B melanoma patients, explained study presenter Jason J. Luke, MD, director of the Cancer Immunotherapeutics Center at UPMC Hillman Cancer Center, Pittsburgh.

Results from the KEYNOTE-716 trial showed that adjuvant pembrolizumab is also beneficial in this earlier stage disease: it improved recurrence-free survival (RFS) by 35% and improved distant metastasis-free survival by 40% compared with placebo.

Adjuvant pembrolizumab is an “effective treatment option with a favorable benefit-risk profile for patients with high-risk stage 2 melanoma,” Dr. Luke concluded.

The manufacturer, Merck, has said that these new results have already been accepted for priority review by the U.S. Food and Drug Administration, making it likely that the indication will be extended to include patients with earlier disease.  

Dr. Luke presented the results at the European Society of Medical Oncology 2021 annual meeting.

Invited discussant Omid Hamid, MD, chief of research/immuno-oncology, the Angeles Clinic and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, said that Dr. Luke’s presentation was “amazing.”

However, these new results have “sabotaged how we think about how we treat our patients and how we’re going to think about what we do in the future.”

Dr. Hamid noted that the incidence of stage 2B and 2C melanoma is “equal” to that of stage 3 disease, “so with a proposed approval” of pembrolizumab in this earlier setting, “we will have a lot more patients” to treat earlier in their disease course.

Of course, this raises the inevitable question of how to treat these patients when they relapse, and how to treat these patients in the metastatic setting “having already exhausted single-agent PD-1 therapy,” he commented.

Dr. Hamid said that the current results also reveal the “current problem” with adjuvant therapy, which is that “we don’t know who benefits,” and there is a subset patients who “never recur” even if they are untreated.

So the questions are: “How come all get treated? What about the risks of toxicity? The costs? And where do we fit these patients into clinic?”

As with so many presentations of immunotherapy trial data, the need for biomarkers was raised, with Dr. Hamid emphasizing the need for predictive biomarkers that could exclude patients, and save them from toxicity.

He noted that there were data with another checkpoint inhibitor, nivolumab (Opdivo), in the adjuvant setting (from the CheckMate 238 trial) that suggested higher tumor mutation burden and tumor interferon-gamma levels could play a role, and he hopes that similar data may be available from this latest trial.

Also, there are ongoing and upcoming trials in patients with stage 2B and 2C melanoma that may answer some of the outstanding questions, including a study of neoadjuvant PD-1 blockade before resection, and the DETECTION trial, which is exploring circulating tumor DNA-guided therapy postsurgery.

Then there is the NivoMela trial that will look at nivolumab in stage 2A as well as 2B and 2C disease, while the REFINE trial will assess whether giving immunotherapy less often to patients with advanced cancer, including those with melanoma, results in fewer side effects while continuing to be effective.

The current results also raise the question of whether to go “earlier and earlier” with adjuvant immunotherapy into “poor risk” stage 1 melanoma, which is already being tried in the United States, although there is “no clear understanding of what to do for those patients.”

Overall, Dr. Hamid said that the results of KEYNOTE-716 have “created more questions than answers,” including its impact on the inclusion criteria for phase 3/4 clinical trials, “which now exclude patients who have received adjuvant therapy within 6 months.”

“That will have to change,” he suggested.

Some of the questions raised by Dr. Hamid were discussed on social media, sparking a lively Twitter debate on how best to take the results forward and into the clinic.

Florentia Dimitriou, MD, a dermatology consultant in the Skin Cancer Clinic, University Hospital Zurich, Switzerland, said the data were “great” but she was “still unclear” over who needs adjuvant immunotherapy in this setting.

She also emphasized that, for her, the greater RFS benefit seen in T3b than in T4b disease “doesn’t make sense,” and she also highlighted the finding of long-term toxicity in approximately 18% of patients.

Dr. Luke replied that he agrees that the T3b/T4b results are puzzling but he said the event rate was “low” and the data are “immature,” and that he hopes to have “more info soon.”

He acknowledged that around 18% of patients taking pembrolizumab went on to receive hormone therapy for adverse events, including 13.9% due to hypothyroidism, and others including hypophysitis, adrenal sufficiency, and type 1 diabetes. However, he also pointed out that about 5% of patients in this study had background thyroid issues. The risks and benefits of treatment need to be discussed with patients, he added.

Over a series of tweets, Rebecca J. Lee, PhD, NIHR clinical lecturer in medical oncology at the University of Manchester, United Kingdom, said, “we need to know more” about the distant metastasis-free survival results, and that results for overall survival are “really” needed.

She also emphasized the need for biomarkers to identify those patients who are likely to benefit, and whether benefit can be upfront or early on in treatment. Dr. Lee added that, as endocrine thyroid toxicity occurs after a median of 3.3 months, “pretreatment biomarkers will be more important than on-treatment biomarkers in this setting.”

Details of the results in earlier stage disease

The KEYNOTE-716 trial enrolled patients with newly diagnosed, resected, high-risk stage 2 melanoma aged ≥ 12 years and a good performance status. The majority (~64%) had stage 2B melanoma, and the rest had stage 2C. T3b disease was present in 41% of patients, 23% had T4a disease, and 35% had T4b disease.

Patients were randomized to receive pembrolizumab or placebo.

In a subsequent part of the study, patients with recurrence will be unblended, with either crossover from the placebo to active treatment group or rechallenge with pembrolizumab for up to 2 years.

Presenting the first part, Dr. Luke said that, of 487 patients assigned to pembrolizumab, 483 started treatment, of whom 206 have completed treatment, 133 are still on therapy, and 144 have discontinued.

In the placebo group, 489 patients were assigned and 486 began treatment. Of those, 229 completed treatment, 152 are still ongoing, and 105 discontinued.

The two groups were well balanced in terms of baseline characteristics. The median age was approximately 60 years, with only one patient enrolled who was aged 12-17 years.

At 12 months, the study met its primary endpoint.

Relapse-fee survival was 90.5% in patients treated with pembrolizumab versus 83.1% in the placebo group, at a hazard ratio for recurrence of 0.65 (P = .00658).

“Despite this trial hitting this primary endpoint very early, there are a number of patients who are censored later in the curves,” Dr. Luke said, adding that “we will continue to see these data mature.”

“In fact, it’s our full expectation that curves will continue to separate over time.”

When looking at key subgroups, Dr. Luke showed that the results favored pembrolizumab when stratifying patients by age, gender, race, and performance status.

Interestingly, patients with T3b disease did a lot better on pembrolizumab compared with those who had T4b disease, at a hazard ratio for recurrence of 0.44 versus 0.94.

Data on recurrence patterns revealed that 11.1% of patients taking pembrolizumab had an event, with 6.4% experiencing skin and/or lymph node regional recurrence and 4.7% distant recurrence.

In the placebo group, 16.8% of patients had a recurrence event, with 8.4% having a loco-regional recurrence and 7.8% a distant recurrence.

Dr. Luke explained that this equates to an approximate 40% reduction in distant recurrence with pembrolizumab over placebo.

Finally, the researchers examined change in global health status on the EORTC QLQ-C30 quality of life score. Examining mean change over time, they found that there were no clinically meaningful changes, and the scores in the pembrolizumab and placebo groups tracked each other during the course of follow-up.

Quality of life was, therefore, “only minimally changed,” Dr. Luke said.

The study was funded by MSD. Dr. Luke and Dr. Hamid have declared relationships with multiple companies.

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

Adjuvant pembrolizumab (Keytruda) following complete melanoma resection could soon move to an earlier stage in the management of high-risk disease, suggest results from KEYNOTE-716. However, the results raise many questions, says an expert invited to discuss the new data.

Adjuvant pembrolizumab is already approved in the United States for use in patients with melanoma with lymph node involvement following complete resection, having been shown to prolong both recurrence-free and distant metastasis-free survival (DMFS) in stage 3 melanoma.

This latest trial involved patients with slightly earlier disease, those with resected stage 2B and 2C melanoma. These patients are at “high risk” of disease recurrence and have similar outcomes to stage 3A and 3B melanoma patients, explained study presenter Jason J. Luke, MD, director of the Cancer Immunotherapeutics Center at UPMC Hillman Cancer Center, Pittsburgh.

Results from the KEYNOTE-716 trial showed that adjuvant pembrolizumab is also beneficial in this earlier stage disease: it improved recurrence-free survival (RFS) by 35% and improved distant metastasis-free survival by 40% compared with placebo.

Adjuvant pembrolizumab is an “effective treatment option with a favorable benefit-risk profile for patients with high-risk stage 2 melanoma,” Dr. Luke concluded.

The manufacturer, Merck, has said that these new results have already been accepted for priority review by the U.S. Food and Drug Administration, making it likely that the indication will be extended to include patients with earlier disease.  

Dr. Luke presented the results at the European Society of Medical Oncology 2021 annual meeting.

Invited discussant Omid Hamid, MD, chief of research/immuno-oncology, the Angeles Clinic and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, said that Dr. Luke’s presentation was “amazing.”

However, these new results have “sabotaged how we think about how we treat our patients and how we’re going to think about what we do in the future.”

Dr. Hamid noted that the incidence of stage 2B and 2C melanoma is “equal” to that of stage 3 disease, “so with a proposed approval” of pembrolizumab in this earlier setting, “we will have a lot more patients” to treat earlier in their disease course.

Of course, this raises the inevitable question of how to treat these patients when they relapse, and how to treat these patients in the metastatic setting “having already exhausted single-agent PD-1 therapy,” he commented.

Dr. Hamid said that the current results also reveal the “current problem” with adjuvant therapy, which is that “we don’t know who benefits,” and there is a subset patients who “never recur” even if they are untreated.

So the questions are: “How come all get treated? What about the risks of toxicity? The costs? And where do we fit these patients into clinic?”

As with so many presentations of immunotherapy trial data, the need for biomarkers was raised, with Dr. Hamid emphasizing the need for predictive biomarkers that could exclude patients, and save them from toxicity.

He noted that there were data with another checkpoint inhibitor, nivolumab (Opdivo), in the adjuvant setting (from the CheckMate 238 trial) that suggested higher tumor mutation burden and tumor interferon-gamma levels could play a role, and he hopes that similar data may be available from this latest trial.

Also, there are ongoing and upcoming trials in patients with stage 2B and 2C melanoma that may answer some of the outstanding questions, including a study of neoadjuvant PD-1 blockade before resection, and the DETECTION trial, which is exploring circulating tumor DNA-guided therapy postsurgery.

Then there is the NivoMela trial that will look at nivolumab in stage 2A as well as 2B and 2C disease, while the REFINE trial will assess whether giving immunotherapy less often to patients with advanced cancer, including those with melanoma, results in fewer side effects while continuing to be effective.

The current results also raise the question of whether to go “earlier and earlier” with adjuvant immunotherapy into “poor risk” stage 1 melanoma, which is already being tried in the United States, although there is “no clear understanding of what to do for those patients.”

Overall, Dr. Hamid said that the results of KEYNOTE-716 have “created more questions than answers,” including its impact on the inclusion criteria for phase 3/4 clinical trials, “which now exclude patients who have received adjuvant therapy within 6 months.”

“That will have to change,” he suggested.

Some of the questions raised by Dr. Hamid were discussed on social media, sparking a lively Twitter debate on how best to take the results forward and into the clinic.

Florentia Dimitriou, MD, a dermatology consultant in the Skin Cancer Clinic, University Hospital Zurich, Switzerland, said the data were “great” but she was “still unclear” over who needs adjuvant immunotherapy in this setting.

She also emphasized that, for her, the greater RFS benefit seen in T3b than in T4b disease “doesn’t make sense,” and she also highlighted the finding of long-term toxicity in approximately 18% of patients.

Dr. Luke replied that he agrees that the T3b/T4b results are puzzling but he said the event rate was “low” and the data are “immature,” and that he hopes to have “more info soon.”

He acknowledged that around 18% of patients taking pembrolizumab went on to receive hormone therapy for adverse events, including 13.9% due to hypothyroidism, and others including hypophysitis, adrenal sufficiency, and type 1 diabetes. However, he also pointed out that about 5% of patients in this study had background thyroid issues. The risks and benefits of treatment need to be discussed with patients, he added.

Over a series of tweets, Rebecca J. Lee, PhD, NIHR clinical lecturer in medical oncology at the University of Manchester, United Kingdom, said, “we need to know more” about the distant metastasis-free survival results, and that results for overall survival are “really” needed.

She also emphasized the need for biomarkers to identify those patients who are likely to benefit, and whether benefit can be upfront or early on in treatment. Dr. Lee added that, as endocrine thyroid toxicity occurs after a median of 3.3 months, “pretreatment biomarkers will be more important than on-treatment biomarkers in this setting.”

Details of the results in earlier stage disease

The KEYNOTE-716 trial enrolled patients with newly diagnosed, resected, high-risk stage 2 melanoma aged ≥ 12 years and a good performance status. The majority (~64%) had stage 2B melanoma, and the rest had stage 2C. T3b disease was present in 41% of patients, 23% had T4a disease, and 35% had T4b disease.

Patients were randomized to receive pembrolizumab or placebo.

In a subsequent part of the study, patients with recurrence will be unblended, with either crossover from the placebo to active treatment group or rechallenge with pembrolizumab for up to 2 years.

Presenting the first part, Dr. Luke said that, of 487 patients assigned to pembrolizumab, 483 started treatment, of whom 206 have completed treatment, 133 are still on therapy, and 144 have discontinued.

In the placebo group, 489 patients were assigned and 486 began treatment. Of those, 229 completed treatment, 152 are still ongoing, and 105 discontinued.

The two groups were well balanced in terms of baseline characteristics. The median age was approximately 60 years, with only one patient enrolled who was aged 12-17 years.

At 12 months, the study met its primary endpoint.

Relapse-fee survival was 90.5% in patients treated with pembrolizumab versus 83.1% in the placebo group, at a hazard ratio for recurrence of 0.65 (P = .00658).

“Despite this trial hitting this primary endpoint very early, there are a number of patients who are censored later in the curves,” Dr. Luke said, adding that “we will continue to see these data mature.”

“In fact, it’s our full expectation that curves will continue to separate over time.”

When looking at key subgroups, Dr. Luke showed that the results favored pembrolizumab when stratifying patients by age, gender, race, and performance status.

Interestingly, patients with T3b disease did a lot better on pembrolizumab compared with those who had T4b disease, at a hazard ratio for recurrence of 0.44 versus 0.94.

Data on recurrence patterns revealed that 11.1% of patients taking pembrolizumab had an event, with 6.4% experiencing skin and/or lymph node regional recurrence and 4.7% distant recurrence.

In the placebo group, 16.8% of patients had a recurrence event, with 8.4% having a loco-regional recurrence and 7.8% a distant recurrence.

Dr. Luke explained that this equates to an approximate 40% reduction in distant recurrence with pembrolizumab over placebo.

Finally, the researchers examined change in global health status on the EORTC QLQ-C30 quality of life score. Examining mean change over time, they found that there were no clinically meaningful changes, and the scores in the pembrolizumab and placebo groups tracked each other during the course of follow-up.

Quality of life was, therefore, “only minimally changed,” Dr. Luke said.

The study was funded by MSD. Dr. Luke and Dr. Hamid have declared relationships with multiple companies.

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

Adjuvant pembrolizumab (Keytruda) following complete melanoma resection could soon move to an earlier stage in the management of high-risk disease, suggest results from KEYNOTE-716. However, the results raise many questions, says an expert invited to discuss the new data.

Adjuvant pembrolizumab is already approved in the United States for use in patients with melanoma with lymph node involvement following complete resection, having been shown to prolong both recurrence-free and distant metastasis-free survival (DMFS) in stage 3 melanoma.

This latest trial involved patients with slightly earlier disease, those with resected stage 2B and 2C melanoma. These patients are at “high risk” of disease recurrence and have similar outcomes to stage 3A and 3B melanoma patients, explained study presenter Jason J. Luke, MD, director of the Cancer Immunotherapeutics Center at UPMC Hillman Cancer Center, Pittsburgh.

Results from the KEYNOTE-716 trial showed that adjuvant pembrolizumab is also beneficial in this earlier stage disease: it improved recurrence-free survival (RFS) by 35% and improved distant metastasis-free survival by 40% compared with placebo.

Adjuvant pembrolizumab is an “effective treatment option with a favorable benefit-risk profile for patients with high-risk stage 2 melanoma,” Dr. Luke concluded.

The manufacturer, Merck, has said that these new results have already been accepted for priority review by the U.S. Food and Drug Administration, making it likely that the indication will be extended to include patients with earlier disease.  

Dr. Luke presented the results at the European Society of Medical Oncology 2021 annual meeting.

Invited discussant Omid Hamid, MD, chief of research/immuno-oncology, the Angeles Clinic and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, said that Dr. Luke’s presentation was “amazing.”

However, these new results have “sabotaged how we think about how we treat our patients and how we’re going to think about what we do in the future.”

Dr. Hamid noted that the incidence of stage 2B and 2C melanoma is “equal” to that of stage 3 disease, “so with a proposed approval” of pembrolizumab in this earlier setting, “we will have a lot more patients” to treat earlier in their disease course.

Of course, this raises the inevitable question of how to treat these patients when they relapse, and how to treat these patients in the metastatic setting “having already exhausted single-agent PD-1 therapy,” he commented.

Dr. Hamid said that the current results also reveal the “current problem” with adjuvant therapy, which is that “we don’t know who benefits,” and there is a subset patients who “never recur” even if they are untreated.

So the questions are: “How come all get treated? What about the risks of toxicity? The costs? And where do we fit these patients into clinic?”

As with so many presentations of immunotherapy trial data, the need for biomarkers was raised, with Dr. Hamid emphasizing the need for predictive biomarkers that could exclude patients, and save them from toxicity.

He noted that there were data with another checkpoint inhibitor, nivolumab (Opdivo), in the adjuvant setting (from the CheckMate 238 trial) that suggested higher tumor mutation burden and tumor interferon-gamma levels could play a role, and he hopes that similar data may be available from this latest trial.

Also, there are ongoing and upcoming trials in patients with stage 2B and 2C melanoma that may answer some of the outstanding questions, including a study of neoadjuvant PD-1 blockade before resection, and the DETECTION trial, which is exploring circulating tumor DNA-guided therapy postsurgery.

Then there is the NivoMela trial that will look at nivolumab in stage 2A as well as 2B and 2C disease, while the REFINE trial will assess whether giving immunotherapy less often to patients with advanced cancer, including those with melanoma, results in fewer side effects while continuing to be effective.

The current results also raise the question of whether to go “earlier and earlier” with adjuvant immunotherapy into “poor risk” stage 1 melanoma, which is already being tried in the United States, although there is “no clear understanding of what to do for those patients.”

Overall, Dr. Hamid said that the results of KEYNOTE-716 have “created more questions than answers,” including its impact on the inclusion criteria for phase 3/4 clinical trials, “which now exclude patients who have received adjuvant therapy within 6 months.”

“That will have to change,” he suggested.

Some of the questions raised by Dr. Hamid were discussed on social media, sparking a lively Twitter debate on how best to take the results forward and into the clinic.

Florentia Dimitriou, MD, a dermatology consultant in the Skin Cancer Clinic, University Hospital Zurich, Switzerland, said the data were “great” but she was “still unclear” over who needs adjuvant immunotherapy in this setting.

She also emphasized that, for her, the greater RFS benefit seen in T3b than in T4b disease “doesn’t make sense,” and she also highlighted the finding of long-term toxicity in approximately 18% of patients.

Dr. Luke replied that he agrees that the T3b/T4b results are puzzling but he said the event rate was “low” and the data are “immature,” and that he hopes to have “more info soon.”

He acknowledged that around 18% of patients taking pembrolizumab went on to receive hormone therapy for adverse events, including 13.9% due to hypothyroidism, and others including hypophysitis, adrenal sufficiency, and type 1 diabetes. However, he also pointed out that about 5% of patients in this study had background thyroid issues. The risks and benefits of treatment need to be discussed with patients, he added.

Over a series of tweets, Rebecca J. Lee, PhD, NIHR clinical lecturer in medical oncology at the University of Manchester, United Kingdom, said, “we need to know more” about the distant metastasis-free survival results, and that results for overall survival are “really” needed.

She also emphasized the need for biomarkers to identify those patients who are likely to benefit, and whether benefit can be upfront or early on in treatment. Dr. Lee added that, as endocrine thyroid toxicity occurs after a median of 3.3 months, “pretreatment biomarkers will be more important than on-treatment biomarkers in this setting.”

Details of the results in earlier stage disease

The KEYNOTE-716 trial enrolled patients with newly diagnosed, resected, high-risk stage 2 melanoma aged ≥ 12 years and a good performance status. The majority (~64%) had stage 2B melanoma, and the rest had stage 2C. T3b disease was present in 41% of patients, 23% had T4a disease, and 35% had T4b disease.

Patients were randomized to receive pembrolizumab or placebo.

In a subsequent part of the study, patients with recurrence will be unblended, with either crossover from the placebo to active treatment group or rechallenge with pembrolizumab for up to 2 years.

Presenting the first part, Dr. Luke said that, of 487 patients assigned to pembrolizumab, 483 started treatment, of whom 206 have completed treatment, 133 are still on therapy, and 144 have discontinued.

In the placebo group, 489 patients were assigned and 486 began treatment. Of those, 229 completed treatment, 152 are still ongoing, and 105 discontinued.

The two groups were well balanced in terms of baseline characteristics. The median age was approximately 60 years, with only one patient enrolled who was aged 12-17 years.

At 12 months, the study met its primary endpoint.

Relapse-fee survival was 90.5% in patients treated with pembrolizumab versus 83.1% in the placebo group, at a hazard ratio for recurrence of 0.65 (P = .00658).

“Despite this trial hitting this primary endpoint very early, there are a number of patients who are censored later in the curves,” Dr. Luke said, adding that “we will continue to see these data mature.”

“In fact, it’s our full expectation that curves will continue to separate over time.”

When looking at key subgroups, Dr. Luke showed that the results favored pembrolizumab when stratifying patients by age, gender, race, and performance status.

Interestingly, patients with T3b disease did a lot better on pembrolizumab compared with those who had T4b disease, at a hazard ratio for recurrence of 0.44 versus 0.94.

Data on recurrence patterns revealed that 11.1% of patients taking pembrolizumab had an event, with 6.4% experiencing skin and/or lymph node regional recurrence and 4.7% distant recurrence.

In the placebo group, 16.8% of patients had a recurrence event, with 8.4% having a loco-regional recurrence and 7.8% a distant recurrence.

Dr. Luke explained that this equates to an approximate 40% reduction in distant recurrence with pembrolizumab over placebo.

Finally, the researchers examined change in global health status on the EORTC QLQ-C30 quality of life score. Examining mean change over time, they found that there were no clinically meaningful changes, and the scores in the pembrolizumab and placebo groups tracked each other during the course of follow-up.

Quality of life was, therefore, “only minimally changed,” Dr. Luke said.

The study was funded by MSD. Dr. Luke and Dr. Hamid have declared relationships with multiple companies.

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

Key clinical point: Diagnostic specificity and sensitivity were high enough to distinguish uterine fibroids (UFs) from adenomyosis when a combination of transvaginal ultrasound (TVUS) and strain ratio (SR) elastography (SE) techniques was implemented.

Major finding: Patients with histologically confirmed UFs vs. those with adenomyosis had a significantly lower mean (5.20±1.81 vs 11.42±1.87) and max (5.78±2.08 vs 13.43±4.10) SR values (both P < .001). Diagnostic sensitivity (90.56% vs. 86.2%) and specificity (96.15% vs 91.37%) were higher for UFs than adenomyosis.

Study details: Findings are from a pilot, prospective study including 79 patients who underwent hysterectomy for suspicion of either UF (n=53) or adenomyosis (n=25), diagnosed on the basis of 2-dimensional TVUS in combination with SE findings.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Săsăran V et al. J Pers Med. 2021 Aug 23. doi: 10.3390/jpm11080824.

Key clinical point: Diagnostic specificity and sensitivity were high enough to distinguish uterine fibroids (UFs) from adenomyosis when a combination of transvaginal ultrasound (TVUS) and strain ratio (SR) elastography (SE) techniques was implemented.

Major finding: Patients with histologically confirmed UFs vs. those with adenomyosis had a significantly lower mean (5.20±1.81 vs 11.42±1.87) and max (5.78±2.08 vs 13.43±4.10) SR values (both P < .001). Diagnostic sensitivity (90.56% vs. 86.2%) and specificity (96.15% vs 91.37%) were higher for UFs than adenomyosis.

Study details: Findings are from a pilot, prospective study including 79 patients who underwent hysterectomy for suspicion of either UF (n=53) or adenomyosis (n=25), diagnosed on the basis of 2-dimensional TVUS in combination with SE findings.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Săsăran V et al. J Pers Med. 2021 Aug 23. doi: 10.3390/jpm11080824.

Key clinical point: Diagnostic specificity and sensitivity were high enough to distinguish uterine fibroids (UFs) from adenomyosis when a combination of transvaginal ultrasound (TVUS) and strain ratio (SR) elastography (SE) techniques was implemented.

Major finding: Patients with histologically confirmed UFs vs. those with adenomyosis had a significantly lower mean (5.20±1.81 vs 11.42±1.87) and max (5.78±2.08 vs 13.43±4.10) SR values (both P < .001). Diagnostic sensitivity (90.56% vs. 86.2%) and specificity (96.15% vs 91.37%) were higher for UFs than adenomyosis.

Study details: Findings are from a pilot, prospective study including 79 patients who underwent hysterectomy for suspicion of either UF (n=53) or adenomyosis (n=25), diagnosed on the basis of 2-dimensional TVUS in combination with SE findings.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Săsăran V et al. J Pers Med. 2021 Aug 23. doi: 10.3390/jpm11080824.

Key clinical point: Hereditary leiomyomatosis and renal cell cancer (HLRCC) can be distinguished from sporadic uterine leiomyomas (ULs) by clinical characteristics and morphologic features of fumarate hydratase (FH)-mutant leiomyomas aided by Bcl-2 and CD34 immunohistochemistry.

Major finding: Women with HLRCC vs. sporadic ULs were significantly younger (33.8 years vs 45.4 years), more frequently symptomatic (95% vs 6.5%), and had numerous ULs (more than 4 tumors, 88.9% vs 30.8%; all P < .0001). Stronger Bcl-2 staining (P = .003) and higher microvessel density highlighted by CD34 immunostaining (P < .0001) distinguished HLRCC-related leiomyomas from sporadic leiomyomas.

Study details: Findings are from a nationwide study including 20 women with a known FH germline mutation and 77 women with sporadic ULs.

Disclosures: This study was supported by the Academy of Finland, Sigrid Jusélius Foundation, Cancer Society of Finland, and Finnish Medical Foundation. The authors declared no conflict of interests.

Source: Uimari O et al. Acta Obstet Gynecol Scand. 2021 Sep 3. doi: 10.1111/aogs.14248.

Key clinical point: Hereditary leiomyomatosis and renal cell cancer (HLRCC) can be distinguished from sporadic uterine leiomyomas (ULs) by clinical characteristics and morphologic features of fumarate hydratase (FH)-mutant leiomyomas aided by Bcl-2 and CD34 immunohistochemistry.

Major finding: Women with HLRCC vs. sporadic ULs were significantly younger (33.8 years vs 45.4 years), more frequently symptomatic (95% vs 6.5%), and had numerous ULs (more than 4 tumors, 88.9% vs 30.8%; all P < .0001). Stronger Bcl-2 staining (P = .003) and higher microvessel density highlighted by CD34 immunostaining (P < .0001) distinguished HLRCC-related leiomyomas from sporadic leiomyomas.

Study details: Findings are from a nationwide study including 20 women with a known FH germline mutation and 77 women with sporadic ULs.

Disclosures: This study was supported by the Academy of Finland, Sigrid Jusélius Foundation, Cancer Society of Finland, and Finnish Medical Foundation. The authors declared no conflict of interests.

Source: Uimari O et al. Acta Obstet Gynecol Scand. 2021 Sep 3. doi: 10.1111/aogs.14248.

Key clinical point: Hereditary leiomyomatosis and renal cell cancer (HLRCC) can be distinguished from sporadic uterine leiomyomas (ULs) by clinical characteristics and morphologic features of fumarate hydratase (FH)-mutant leiomyomas aided by Bcl-2 and CD34 immunohistochemistry.

Major finding: Women with HLRCC vs. sporadic ULs were significantly younger (33.8 years vs 45.4 years), more frequently symptomatic (95% vs 6.5%), and had numerous ULs (more than 4 tumors, 88.9% vs 30.8%; all P < .0001). Stronger Bcl-2 staining (P = .003) and higher microvessel density highlighted by CD34 immunostaining (P < .0001) distinguished HLRCC-related leiomyomas from sporadic leiomyomas.

Study details: Findings are from a nationwide study including 20 women with a known FH germline mutation and 77 women with sporadic ULs.

Disclosures: This study was supported by the Academy of Finland, Sigrid Jusélius Foundation, Cancer Society of Finland, and Finnish Medical Foundation. The authors declared no conflict of interests.

Source: Uimari O et al. Acta Obstet Gynecol Scand. 2021 Sep 3. doi: 10.1111/aogs.14248.

Key clinical point: Ovarian arteries embolization (OAE) improved quality of life (QoL) and lowered rates of subsequent surgery in women who experienced persistent symptoms after uterine arteries embolization (UAE) for uterine fibroids (UF).

Major finding: Less than a fifth of the cohort underwent subsequent hysterectomy. Almost 90.9% of patients who underwent magnetic resonance imaging after 12 months of OAE showed a decrease in uterine volume and complete devascularization of the dominant fibroid tumor. After a mean follow-up of 70 months, 8 of the 10 patients who responded to the QoL questionnaire reported an improvement or stability of symptoms.

Study details: Findings are from a retrospective analysis of 1,300 women treated with UAE for symptomatic UF, of which 18 women underwent a second embolization through one or both ovarian arteries.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Ifergan H et al. Abdom Radiol (NY). 2021 Aug 25. doi: 10.1007/s00261-021-03255-w.

Key clinical point: Ovarian arteries embolization (OAE) improved quality of life (QoL) and lowered rates of subsequent surgery in women who experienced persistent symptoms after uterine arteries embolization (UAE) for uterine fibroids (UF).

Major finding: Less than a fifth of the cohort underwent subsequent hysterectomy. Almost 90.9% of patients who underwent magnetic resonance imaging after 12 months of OAE showed a decrease in uterine volume and complete devascularization of the dominant fibroid tumor. After a mean follow-up of 70 months, 8 of the 10 patients who responded to the QoL questionnaire reported an improvement or stability of symptoms.

Study details: Findings are from a retrospective analysis of 1,300 women treated with UAE for symptomatic UF, of which 18 women underwent a second embolization through one or both ovarian arteries.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Ifergan H et al. Abdom Radiol (NY). 2021 Aug 25. doi: 10.1007/s00261-021-03255-w.

Key clinical point: Ovarian arteries embolization (OAE) improved quality of life (QoL) and lowered rates of subsequent surgery in women who experienced persistent symptoms after uterine arteries embolization (UAE) for uterine fibroids (UF).

Major finding: Less than a fifth of the cohort underwent subsequent hysterectomy. Almost 90.9% of patients who underwent magnetic resonance imaging after 12 months of OAE showed a decrease in uterine volume and complete devascularization of the dominant fibroid tumor. After a mean follow-up of 70 months, 8 of the 10 patients who responded to the QoL questionnaire reported an improvement or stability of symptoms.

Study details: Findings are from a retrospective analysis of 1,300 women treated with UAE for symptomatic UF, of which 18 women underwent a second embolization through one or both ovarian arteries.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Ifergan H et al. Abdom Radiol (NY). 2021 Aug 25. doi: 10.1007/s00261-021-03255-w.

Key clinical point: The surgical approach for removal of uterine fibroids should consider the number and size of fibroids, surgical time, and reproductive diagnosis with minimally invasive routes offered whenever possible because of its better outcome on achieving pregnancy.

Major finding: Laparotomic myomectomy was favored when the number (P = .000) and weight (P = .004) of fibroids were considered. Robotic surgery took a longer time than others (P = .00). When the impact of number of fibroids on achieving pregnancy was analyzed, both groups with lesser (P = .017) and greater (P < .001) than 6 fibroids preferred minimally invasive routes like laparoscopic or robotic surgery.

Study details: Findings are from a retrospective, cross-sectional study including 69 patients with infertility who underwent myomectomy approaches, of which 21, 24, and 24 patients underwent laparotomy, conventional laparoscopy, and robotic-assisted laparoscopy, respectively.

Disclosures: No information on funding was available. The authors declared no conflict of interests.

Source: Morales HSG et al. JBRA Assist Reprod. 2021 Aug 20. doi: 10.5935/1518-0557.20210049.

Key clinical point: The surgical approach for removal of uterine fibroids should consider the number and size of fibroids, surgical time, and reproductive diagnosis with minimally invasive routes offered whenever possible because of its better outcome on achieving pregnancy.

Major finding: Laparotomic myomectomy was favored when the number (P = .000) and weight (P = .004) of fibroids were considered. Robotic surgery took a longer time than others (P = .00). When the impact of number of fibroids on achieving pregnancy was analyzed, both groups with lesser (P = .017) and greater (P < .001) than 6 fibroids preferred minimally invasive routes like laparoscopic or robotic surgery.

Study details: Findings are from a retrospective, cross-sectional study including 69 patients with infertility who underwent myomectomy approaches, of which 21, 24, and 24 patients underwent laparotomy, conventional laparoscopy, and robotic-assisted laparoscopy, respectively.

Disclosures: No information on funding was available. The authors declared no conflict of interests.

Source: Morales HSG et al. JBRA Assist Reprod. 2021 Aug 20. doi: 10.5935/1518-0557.20210049.

Key clinical point: The surgical approach for removal of uterine fibroids should consider the number and size of fibroids, surgical time, and reproductive diagnosis with minimally invasive routes offered whenever possible because of its better outcome on achieving pregnancy.

Major finding: Laparotomic myomectomy was favored when the number (P = .000) and weight (P = .004) of fibroids were considered. Robotic surgery took a longer time than others (P = .00). When the impact of number of fibroids on achieving pregnancy was analyzed, both groups with lesser (P = .017) and greater (P < .001) than 6 fibroids preferred minimally invasive routes like laparoscopic or robotic surgery.

Study details: Findings are from a retrospective, cross-sectional study including 69 patients with infertility who underwent myomectomy approaches, of which 21, 24, and 24 patients underwent laparotomy, conventional laparoscopy, and robotic-assisted laparoscopy, respectively.

Disclosures: No information on funding was available. The authors declared no conflict of interests.

Source: Morales HSG et al. JBRA Assist Reprod. 2021 Aug 20. doi: 10.5935/1518-0557.20210049.