1207O Bevacizumab + erlotinib vs erlotinib alone as first-line treatment of pts with EGFR mutated advanced non squamous NSCLC: Final analysis of the multicenter, randomized, phase III BEVERLY trial

Abstract

Adding bevacizumab to erlotinib prolonged PFS in NEJ026 and CTONG 1509 trials, but limited data are available in non-Asian patients (pts). BEVERLY is an Italian no-profit, randomized, open-label, multicenter phase III trial of bevacizumab (BEV) plus erlotinib (E) vs E alone as first-line treatment for EGFR-mutated advanced NSCLC. Eligible pts were randomized 1:1 to E (150mg daily) alone or combined with BEV (15mg/kg iv q3w) until disease progression or unacceptable toxicity. Center, ECOG PS and type of mutation (ex19 deletion vs ex21 L858R vs others) were stratification variables. Co-primary endpoints were investigator-assessed PFS (IA-PFS) and blinded-independent centrally-reviewed PFS (BICR-PFS). Secondary endpoints were OS, QoL, IA- and BICR- objective response rate (ORR) and safety; biomarker analyses are also planned. 126 events out of 160 randomized pts were required to detect a PFS prolongation with BEV from 10 to 16.7 mos (HR 0.60), with 2-sided α=0.05, 80% power. From Apr 11, 2016 to Feb 27, 2019, 160 pts were randomized to BEV+E (80) or E alone (80). Pts were mainly female (63.8%), never smokers (51.9%), ECOG PS 0-1 (98.1%), median age 66 (IQR 59-73); 55% of pts had ex19Del and 41% L858R mutation. At a median follow-up of 31 mos, 130/160 (81.3%) pts had a PFS event (progression or death) and 84/160 (52.5%) died. BEV+E significantly prolonged IA-PFS over E alone with a median of 15.4 vs 9.7 mos (HR 0.60; 95%CI 0.42-0.85, log-rank P=0.0039). Median OS was 28.4 vs 23.0 mos in BEV+E and E arms, respectively (HR 0.70; 95%CI 0.46-1.10, log-rank P=0.12). One toxic death was reported, due to intracranial hemorrhage with BEV+E. Hypertension (any grade: 49% vs 18%; 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%) were more frequent with the experimental combination treatment. The addition of BEV to E significantly prolonged IA-PFS compared with E alone as first-line treatment in Italian EGFR-mutated NSCLC patients, with no unexpected safety issues. Blinded radiologic revision of PFS and ORR is ongoing and will be presented at the meeting.