982P Final results and biomarker analysis 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

Previous studies showed that the addition of anti-VEGF inhibitors to erlotinib prolonged progression-free survival (PFS) in EGFR mutated non-squamous non-small-cell lung cancer (Ns-NSCLC) patients (pts). The primary results of WJOG9717L study, open-label, randomized phase II trial comparing Osimertinib (Osi) plus bevacizumab (Bev) with Osi monotherapy for untreated pts with advanced EGFR mutated Ns-NSCLC, were reported at ESMO2021. 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), and was updated. In exploratory analysis using tissue (pretreatment) and plasma samples (at baseline, cycles 2 and cycle 9), 197 genes were evaluated by targeted deep sequencing. Between January 2018 and September 2018, 122 pts were enrolled (OB arm, 61 pts O arm, 61 pts). At a median follow-up of 36 months, median updated PFS by BICR was 22.1 months for OB arm and 20.2 months for O arm, with a hazard ratio (HR) of 0.864 (60% CI, 0.711–1.049; 95% CI, 0.549–1.359; one-sided stratified log-rank p=0.202). Updated overall survival (OS) was also not different between two arms with a HR of 1.271 (95% CI, 0.727–2.233) (median OS 33.3 months for OB arm, and 36.5 months for O arm). Among those patients, 94 had evaluable plasma samples at baseline, and 40 had evaluable pretreatment tissue samples. EGFR mutations (76.6%), TP53 mutations (44.7%), EGFR CNV (54.3%) and MET CNV (19.1%) were detected in plasma samples at baseline. In subgroup of patients with TP53 mutations (N=42), median PFS by BICR was 19.8 months for OB arm and 20.2 months for O arm, with a HR of 1.107 (95% CI, 0.534–2.297). There was also no significant difference in updated PFS between OB arm and O arm, even in patients with TP53 mutations.