No overall survival benefit with first-line bevacizumab–erlotinib in EGFR-mutant NSCLC
medwireNews: The addition of bevacizumab to erlotinib does not improve the overall survival (OS) of treatment-naïve patients with advanced non-small-cell lung cancer (NSCLC) harboring an activating EGFR mutation, NEJ026 study data show.
An interim analysis of the phase 3 trial – previously reported by medwireNews – showed that progression-free survival was significantly longer with bevacizumab plus erlotinib than erlotinib alone in Japanese patients with stage IIIB–IV or recurrent nonsquamous NSCLC and an EGFR exon 19 deletion or exon 21 Leu858Arg point mutation.
However, the current analysis, conducted at a median follow-up of 39.2 months, did not show a significant difference in OS between the 112 patients who were randomly assigned to receive bevacizumab 15 mg/kg every 21 days plus erlotinib 150 mg once a day and the 112 who received erlotinib alone, at a median of 50.7 and 46.2 months, respectively.
“Why the addition of bevacizumab to erlotinib did not affect overall survival is unclear, but it is possible that the beneficial effects of combination therapy were not seen because overall survival was influenced by treatment regimens used after disease progression,” say Makoto Maemondo (Iwate Medical University School of Medicine, Yahaba, Japan) and colleagues in The Lancet Respiratory Medicine.
Specifically, 75.9% of patients in the combination arm received a second-line treatment as did 83.0% of those in the erlotinib monotherapy arm, most commonly osimertinib (27.7 and 25.9%, respectively), platinum-based chemotherapy plus pemetrexed (29.5 and 16.1%), and platinum-based chemotherapy plus pemetrexed and bevacizumab (4.5 and 28.6%).
The investigators also performed an exploratory analysis of time from enrolment to progressive disease during second-line treatment or death, which was “slightly longer” in the combination versus monotherapy group, at a median of 28.6 and 24.3 months, respectively, albeit without reaching statistical significance.
Maemondo et al note that there are three ongoing phase 3 trials of VEGF- and VEGFR-targeted monoclonal antibodies with EGFR–tyrosine kinase inhibitors in patients with advanced EGFR-mutated NSCLC, namely the BEVERLY and CTONG 1509 trials of bevacizumab plus erlotinib and the RELAY trial of ramucirumab plus erlotinib.
“The overall survival results from these studies will help to will help to establish whether this treatment strategy is optimal” in this patient population, they conclude.
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