In an analysis of more than 3000 randomized controlled trials, researchers identified 396 medical reversals — a total that included what investigators determined were 23 oncology reversals and 8 reversals related to cancer in the context of preventive medicine.1 Of the oncology reversals, 3 focused specifically on the use of bevacizumab in glioblastoma.
In 2009, bevacizumab received accelerated approval from the US Food and Drug Administration (FDA) to treat progressive glioblastoma following prior therapy.2 The FDA then granted bevacizumab regular approval for treatment of recurrent glioblastoma in adults in 20173— nearly 3 weeks following the publication of confirmatory trial results that showed that adding bevacizumab to lomustine did not improve overall survival compared with lomustine alone in patients with progressive glioblastoma.4 Overall survival was the primary end point of that study, and that end point was ultimately not met — leading the researchers to list this 2017 study as 1 of the 3 reversals related to the use of bevacizumab in glioblastoma.
The study of lomustine and bevacizumab (ClinicalTrials.gov Identifier: NCT01290939; Study Identifier: EORTC-26101) involved 437 patients. The addition of bevacizumab did result in “somewhat prolonged progression-free survival,” noted the study authors in that paper.4 Specifically, progression-free survival — one of the study’s secondary end points — was 4.2 months in the combination therapy group versus 1.5 months in the lomustine monotherapy group. However, a greater proportion of patients in the combination group (63.6%) experienced grade 3 to grade 5 adverse events compared with the monotherapy group (38.1%). In addition, bevacizumab did not improve neurocognitive functioning or health-related quality of life.4
“[T]his study, by all accounts, was negative,” said Jennifer Gill, MS, a research assistant at Oregon Health & Science University in Portland, who coauthored the new analysis of medical reversals. “Patients don’t live longer or feel better from the addition of bev in this setting.”
“Although the study failed to demonstrate an overall survival (OS) benefit, the progression-free survival (PFS) for patients receiving bevacizumab plus lomustine compared with the lomustine alone was consistent with the improved PFS seen in 2 other large randomized trials in patients with [glioblastoma],” an FDA spokesperson wrote to Cancer Therapy Advisor.