First-Line Bevacizumab Plus Erlotinib Prolongs PFS in EGFR-Mutated Advanced NSCLC: BEVERLY Trial

Findings from the BEVERLY trial provide evidence of progression-free survival (PFS) improvement with the addition of bevacizumab to erlotinib as first-line therapy in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC).

“Adding bevacizumab to erlotinib prolonged PFS of patients with EGFR-mutated advanced NSCLC in the Japanese JO25567 trial, but limited data were available in non-Asian patients,” explained Maria Carmela Piccirillo, MD, Clinical Trial Unit, Istituto Nazionale Tumori – IRCCS – Fondazione G. Pascale, Napoli and colleagues.

This lead Dr Piccirillo et al to conduct the phase 3 BEVERLY trial, which is a randomized, open-label, multicenter trial of bevacizumab plus erlotinib vs erlotinib alone as first-line treatment for EGFR-mutated advanced NSCLC.

A total of 160 patients were randomized in a 1:1 ratio to receive to erlotinib plus bevacizumab (n = 80) or erlotinib alone (n = 80). Erlotinib dose was 150 mg orally once daily in both arms; bevacizumab, 15 mg/kg intravenously, was given every 21 days.

The coprimary end points were investigator-assessed PFS and blinded-independent centrally reviewed PFS. With 80% power in detecting a 0.60 hazard ratio (HR) and 2–sided α error 0.05, 126 events out of 160 patients were needed.

At a median follow-up of 36.3 months, median investigator-assessed PFS was 15.4 months (95% confidence interval [CI], 12.2 to 18.6) with erlotinib plus bevacizumab and 9.6 months (95% CI, 8.2 to 10.6) with erlotinib alone (HR, 0.66; 95% CI, 0.47 to 0.92). blinded-independent centrally reviewed PFS analysis confirmed this result.

Researchers noted a statistically significant interaction with treatment effect was found for smoking habit (P = .0323), with PFS prolongation being clinically significant only among current or previous smokers.

Adverse events included hypertension (grade ≥3: 24% vs 5%), skin rash (grade ≥3: 31% vs 14%), thromboembolic events (any grade: 11% vs 4%), and proteinuria (any grade: 23% vs 6%), all of which were more frequent with the combination.

“The addition of bevacizumab to first-line erlotinib prolonged PFS in Italian patients with EGFR-mutated NSCLC; toxicity was increased with the combination but without unexpected safety issues.”, concluded Dr Piccirillo and colleagues.

Source:

Piccirillo MC, Bonanno L, Garassino MC, et al. Addition of bevacizumab to erlotinib as first-line treatment of patients with EGFR-mutated advanced nonsquamous non-small cell lung cancer. The BEVERLY multicenter randomized phase III trial. J Thorac Oncol. 2022;S1556-0864(22)00268-4. doi:10.1016/j.jtho.2022.05.008