Continuation of Bevacizumab After Progression May Not Improve Survival Outcomes in NSCLC

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AvaALL was the first phase 3 study to evaluate bevacizumab across multiple lines of treatment beyond progression in patients with non-small cell lung cancer.
AvaALL was the first phase 3 study to evaluate bevacizumab across multiple lines of treatment beyond progression in patients with non-small cell lung cancer.

Bevacizumab continuation post-disease progression does not improve survival outcomes among patients with non-small cell lung cancer (NSCLC), according to a study published in JAMA Oncology.1

Previous studies have explored the benefits to progression-free survival (PFS) and overall survival (OS) with bevacizumab continuation therapy among patients with NSCLC, but results have been mixed and require further confirmation.

For the AvaALL phase 3 study (ClinicalTrials.gov Identifier: NCT01351415), researchers randomly assigned 485 patients with nonsquamous NSCLC to receive bevacizumab plus standard of care chemotherapy (SOC) or SOC alone beyond first progression. AvaALL was the first phase 3 study to evaluate bevacizumab across multiple lines of treatment beyond disease progression. Patients were previously treated with first-line bevacizumab plus platinum-doublet chemotherapy and at least 2 cycles of bevacizumab. 

Results showed that although median OS was longer for patients in the bevacizumab arm plus SOC, it was not significantly longer compared with patients in the SOC alone arm (11.9 vs 10.2 months; hazard ratio [HR], 0.84; 90% CI, 0.71-1.00; P = .104).

Secondary outcomes, such as PFS from randomization at first progression to second (PFS2) and third progression (PFS3); and time to progression (TTP) from randomization at first progression to second (TTP2) and third progression (TTP3); were all numerically prolonged among patients treated with bevacizumab, but only significantly improved for PFS3, TTP2, and TTP3.

Grade 3 to grade 4 adverse events (AEs) were reported more frequently in the bevacizumab plus SOC arm compared with the SOC alone arm (76.5% vs 60.3%), and included fatigue, asthenia, diarrhea, nausea, anemia, and dyspnea. AEs of special interest, such as thromboembolic events, hypertension, and proteinuria, also occurred with greater frequency in the bevacizumab plus SOC arm compared with SOC alone (48.6% vs 27.2%, respectively).   

The authors concluded that “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.”

Reference

  1. Gridelli C, de Castro Carpeno J, Dingemans AMC, et al. Safety and efficacy of bevacizumab plus standard-of-care treatment beyond disease progression in patients with advanced non-small cell lung cancer [published online August 30, 2018]. JAMA Oncol. doi: 10.1001/jamaoncol.2018.3486

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