LBA44 Primary results of a randomized phase II study of osimertinib plus bevacizumab versus osimertinib monotherapy for untreated patients with non-squamous non-small cell lung cancer harboring EGFR mutations: WJOG9717L study

Osimertinib (Osi) has been a standard treatment for untreated patients (pts) with non-small-cell lung cancer (NSCLC) harboring an EGFR mutation. Previous studies showed that the addition of anti-VEGF inhibitors to erlotinib prolonged progression-free survival (PFS) in EGFR mutated non-squamous NSCLC (Ns-NSCLC) pts. This phase II, open-label, randomized trial was conducted to compare Osi plus bevacizumab (Bev) with Osi monotherapy for untreated pts with advanced EGFR mutated Ns-NSCLC. This study enrolled untreated pts with advanced Ns-NSCLC harboring an EGFR sensitizing mutation (Del19 or L858R), and without symptomatic brain metastases. 122 eligible pts were randomized in a 1:1 ratio to receive either Osi (80 mg, daily) plus Bev (15 mg/kg, every 3 weeks) (OB arm) or Osi monotherapy (O arm), and stratified according to sex, stage and EGFR mutation status. The primary endpoint was PFS, assessed by blinded, independent central radiologic reviewer (BICR). Assuming that the median PFS in the OB arm and the O arm were 27 and 18 months, planned sample size was 120 in total to give a power of 80% with a one-sided alpha of 20%, with an accrual period of 1.5 years and a follow-up period of 2 years. Between January 2018 and September 2018, 122 pts were enrolled (OB arm, 61 pts O arm, 61 pts). At a median follow-up of 19.8 months, median PFS by BICR was 22.1 months for OB arm and 20.2 months for O arm, with a hazard ratio (HR) of 0.862 (60% CI, 0.700–1.060; 95% CI, 0.531–1.397; one-sided stratified log-rank p=0.213). In subgroup analysis, ex-smoker (HR 0.481) and pts with 19del (HR 0.622) showed better trend of PFS in OB arm. Objective response rate was 82% in OB arm and 86% in O arm. Grade 3-4 adverse events were observed in 34 pts (56%) for OB arm and in 29 (48%) for O arm. Any grade paronychia, rash acneiform, hypertension, epistaxis and proteinuria were frequently observed in OB arm. Among them, 3% and 18% experienced any grade pneumonitis, and grade 3 pneumonitis in 1 pt for each arm. This study failed to show the efficacy of OB arm for improving PFS in untreated pts with EGFR mutated Ns-NSCLC.