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ASCO 2021 | Nivolumab plus bevacizumab in recurrent glioblastoma

Yasmeen Rauf, MD, Cleveland Clinic, Cleveland, OH, talks on the findings of a Phase II study (NCT03452579) of nivolumab with standard or reduced dose bevacizumab in recurrent glioblastoma. VEGF is overexpressed in glioblastoma and contributes to tumor-associated immunosuppression. Thus, combining an anti-PD1 agent with a VEGF-targeting agent may be a promising strategy to improve its efficacy. 90 patients were randomized to receive nivolumab with bevacizumab at either 10mg/kg (standard dose) or 3mg/kg (low dose). After a median follow-up of 7.7 months, no significant difference was seen in overall survival across the two dose levels. Survival rates were comparable to reported data with bevacizumab monotherapy. When participants were assessed by age, overall survival was better with standard dose bevacizumab compared to low dose in patients over 60. The trial results suggest that older patients may benefit from combined nivolumab and standard-dose bevacizumab. This interview took place at the American Society of Clinical Oncology (ASCO) 2021 Virtual Meeting.

Transcript (edited for clarity)

This was a randomized phase two open-label study of nivolumab plus standard-dose bevacizumab versus nivolumab plus low-dose bevacizumab in patients with recurrent glioblastoma. So as you guys all know, nivolumab is targeted therapy for PD-1 mediated immunosuppression, and has shown a clinical benefit among other cancers. Bevacizumab is a VEGF inhibitor, which has already been FDA approved for recurrent glioblastoma...

This was a randomized phase two open-label study of nivolumab plus standard-dose bevacizumab versus nivolumab plus low-dose bevacizumab in patients with recurrent glioblastoma. So as you guys all know, nivolumab is targeted therapy for PD-1 mediated immunosuppression, and has shown a clinical benefit among other cancers. Bevacizumab is a VEGF inhibitor, which has already been FDA approved for recurrent glioblastoma. The primary endpoint of this study was to evaluate the efficacy of nivolumab when administered with standard and reduced-dose bevacizumab in patients who had a recurrence of their glioblastoma.

So the primary objective was to check the overall survival between these two arms in this patient population. The secondary objective was to evaluate the safety and tolerability of nivolumab in combination with bevacizumab and to compare the progression-free survival at six months of nivolumab with the standard dose, and compare it with those who received the reduced dosing of bevacizumab.

90 patients were enrolled in the study between May 2018 and January 2020. And like I mentioned, this study had two arms, both arms received the same dose of nivolumab, which was 250 milligrams IV every two weeks. And arm A received bevacizumab at 10 milligrams per kg IV every two weeks, arm B received three milligrams per kg IV every two weeks, of bevacizumab.

The characteristics in both arms were similar. Age was about 20, about 60 and a half years. The median KPS was 80. We had 35 patients that were MGMT methylated and 53 that were MGMT not hypermethylated. The median overall survival was 9 months for arm A and 9.7 months for arm B. The overall survival at one year was 41.1% for arm A and 37.7% for arm B. The progression-free survival was 5.6 months for arm A and 4.6 months for arm B. Progression-free survival six month rate was 46.7% for arm A and 44.6% for arm B.

So the PFS and OS rates appeared similar for nivolumab with either standard or low-dose bevacizumab, and compared to the historical benchmarks of bevacizumab monotherapy. However, when we did our analysis and differentiated these patients based on age, we realized that the overall survival was better in patients who were less than 60 years of age. So with the study, we kind of concluded that there may be some benefit of giving nivolumab to patients with recurrent glioblastoma who were less than 60 years of age.

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