Does the Addition of Bevacizumab to Erlotinib in Advanced EGFR-Mutant NSCLC Improve PFS?

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In a phase II trial reported in JAMA OncologyThomas E. Stinchcombe, MD, and colleagues found that the addition of bevacizumab to erlotinib did not significantly improve progression-free survival (PFS) in patients with advanced EGFR-mutant non–small cell lung cancer (NSCLC).

Thomas E. Stinchcombe, MD

Thomas E. Stinchcombe, MD

Study Details

The multicenter study included 88 patients with an EGFR exon 19 deletion or exon 21 L858R mutation and stage IV NSCLC who were eligible for treatment with bevacizumab and who had received no systemic therapy for stage IV disease. Patients were randomly assigned between November 2012 and August  2016 to receive erlotinib 150 mg daily plus bevacizumab 15 mg/kg every 3 weeks (n = 43) or erlotinib alone (n = 45). Treatment continued until disease progression or unacceptable toxicity.

The primary endpoint was progression-free survival.

Progression-Free Survival

Median follow-up was 33 months. Median progression-free survival was 17.9 months in the combination group vs 13.5 months in the erlotinib group (hazard ratio [HR] = 0.81, P = .39). Objective response rates were 81% vs 83% (P = .81). Median overall survival was 32.4 months vs 50.6 months (HR = 1.41, P = .33). Data were not systematically collected on poststudy treatment therapy, which was given at the discretion of investigators; among patients with available data, osimertinib was received by 10 patients in the combination group and 13 patients in the erlotinib group. 


  • The addition of bevacizumab to erlotinib did not significantly improve progression-free survival.
  • No significant differences were observed in response rate or overall survival.

Adverse Events

The most common adverse events of grade ≥ 3 occurring in five or more patients in the combination vs erlotinib groups were hypertension (40% vs 20%), skin eruption (26% vs 16%), proteinuria (12% vs 0%), and diarrhea (9% vs 13%). Adverse events led to discontinuation of treatment in 26% of the combination group, with the most frequent treatment-related causes being skin eruption (7%) and hypertension (7%).  

The investigators concluded, “Erlotinib plus bevacizumab compared with erlotinib did not result in a significant improvement in [progression-free survival] in EGFR-mutant NSCLC.”

Thomas E. Stinchcombe, MD, of the Duke Cancer Institute, Duke University Medical Center, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was supported by Genentech/Roche. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.