Bevacizumab Treatment Beyond Disease Progression in Advanced NSCLC
As reported in JAMA Oncology by Gridelli et al, the phase IIIB AvaALL trial did not show improved overall survival with continued bevacizumab (Avastin) treatment beyond disease progression in patients with advanced non–small cell lung cancer (NSCLC), although some improvements in subsequent progression-free survival and time to disease progression were observed.
Study Details
In the open-label trial, conducted between 2011 and 2015, 485 patients with nonsquamous NSCLC from 123 sites worldwide were randomized to continued bevacizumab plus standard of care (n = 245) or standard of care (n = 240) after disease progression on first-line bevacizumab plus platinum-doublet chemotherapy and at least two cycles of bevacizumab maintenance. Patients received bevacizumab at 7.5 or 15 mg/kg every 21 days and investigator choice of standard of care.
The primary outcome measure was overall survival after first disease progression. Secondary outcomes included progression-free survival from first to second (PFS2) and third disease progression (PFS3), as well as time to second (TTP2) and third disease progression (TTP3).
Efficacy Outcomes
Median overall survival after first disease progression was 11.9 months with continued bevacizumab/standard of care vs 10.2 months with continued standard of care (hazard ratio = 0.84, P = .104). Median PFS2 was 5.5 vs 4.0 months (HR = 0.83, P = .06) and median PFS3 was 4.0 vs 2.6 months (HR = 0.63, P = .0045). Median TTP2 was 5.6 vs 4.2 months (HR = 0.79, P = .0311) and median TTP3 was 4.1 vs 2.7 months (HR = 0.69, P = .0326).
Toxicity
The frequency of adverse events of special interest of any grade, consisting of arterial and venous thromboembolic events, hypertension, and proteinuria, was 48.6% in the bevacizumab/standard of care group vs 27.2 in the standard of care group. Grade 3 or 4 adverse events occurred in 76.5% vs 60.3%. Death due to adverse events considered related to treatment occurred in 6.6% vs 5.2%. No new bevacizumab safety signals were observed.
The investigators concluded, “A substantial benefit of bevacizumab therapy beyond progression in patients with NSCLC was not shown, but some improvements in efficacy were observed. No new safety signals were identified.”
The study was funded by F. Hoffmann-La Roche Ltd.
Cesare Gridelli, MD, of the Division of Medical Oncology, S.G. Moscati Hospital, Avellino, is the corresponding author of the JAMA Oncology article.
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