Introduction: Adding bevacizumab to erlotinib prolonged progression-free survival (PFS) of patients with EGFR-mutated advanced NSCLC in the Japanese JO25567 trial, but limited data were available in non-Asian patients. BEVERLY is an Italian, multicenter, randomized, phase 3 investigating the addition of bevacizumab to erlotinib as first-line treatment of advanced EGFR-mutated NSCLC.Methods: Eligible patients were randomized 1:1 to erlotinib plus bevacizumab or erlotinib alone. Investigator-assessed PFS and blinded independent centrally reviewed PFS were coprimary end points. With 80% power in detecting a 0.60 hazard ratio and two-sided a error of 0.05, 126 events of 160 patients were needed. The trial was registered as NCT02633189 and EudraCT 2015-002235-17.Results: From April 11, 2016, to February 27, 2019, a total of 160 patients were randomized to erlotinib plus bevacizumab (80) or erlotinib alone (80). At a median follow-up of 36.3 months, median investigator-assessed PFS was 15.4 months (95% confidence interval [CI]: 12.2-18.6) with erlotinib plus bevacizumab and 9.6 months (95% CI: 8.2-10.6) with erlotinib alone (hazard ratio = 0.66, 95% CI: 0.47-0.92). Blinded independent centrally reviewed PFS analysis confirmed this result. A statistically significant interaction with treatment effect was found for smoking habit (p = 0.0323), with PFS prolongation being clinically significant only among current or previous smokers. Hypertension (grade >3: 24% versus 5%), skin rash (grade > 3: 31% versus 14%), thromboembolic events (any grade: 11% versus 4%), and proteinuria (any grade: 23% versus 6%) were more frequent with the combination.Conclusions: The addition of bevacizumab to first-line erlotinib prolonged PFS in Italian patients with EGFRmutated NSCLC; toxicity was increased with the combination but without unexpected safety issues. (C) 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc.
Addition of Bevacizumab to Erlotinib as First-Line Treatment of Patients With EGFR-Mutated Advanced Nonsquamous NSCLC: The BEVERLY Multicenter Randomized Phase 3 Trial
Tonini, Giuseppe;
2022-01-01
Abstract
Introduction: Adding bevacizumab to erlotinib prolonged progression-free survival (PFS) of patients with EGFR-mutated advanced NSCLC in the Japanese JO25567 trial, but limited data were available in non-Asian patients. BEVERLY is an Italian, multicenter, randomized, phase 3 investigating the addition of bevacizumab to erlotinib as first-line treatment of advanced EGFR-mutated NSCLC.Methods: Eligible patients were randomized 1:1 to erlotinib plus bevacizumab or erlotinib alone. Investigator-assessed PFS and blinded independent centrally reviewed PFS were coprimary end points. With 80% power in detecting a 0.60 hazard ratio and two-sided a error of 0.05, 126 events of 160 patients were needed. The trial was registered as NCT02633189 and EudraCT 2015-002235-17.Results: From April 11, 2016, to February 27, 2019, a total of 160 patients were randomized to erlotinib plus bevacizumab (80) or erlotinib alone (80). At a median follow-up of 36.3 months, median investigator-assessed PFS was 15.4 months (95% confidence interval [CI]: 12.2-18.6) with erlotinib plus bevacizumab and 9.6 months (95% CI: 8.2-10.6) with erlotinib alone (hazard ratio = 0.66, 95% CI: 0.47-0.92). Blinded independent centrally reviewed PFS analysis confirmed this result. A statistically significant interaction with treatment effect was found for smoking habit (p = 0.0323), with PFS prolongation being clinically significant only among current or previous smokers. Hypertension (grade >3: 24% versus 5%), skin rash (grade > 3: 31% versus 14%), thromboembolic events (any grade: 11% versus 4%), and proteinuria (any grade: 23% versus 6%) were more frequent with the combination.Conclusions: The addition of bevacizumab to first-line erlotinib prolonged PFS in Italian patients with EGFRmutated NSCLC; toxicity was increased with the combination but without unexpected safety issues. (C) 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
