INTRODUCTIONEGFR tyrosine kinase inhibitors have been a standard treatment for patients with non-small cell lung cancer (NSCLC) have sensitive EGFR mutations. This study showed final analysis survival data, biomarkers and resistance mechanisms of osimertinib plus bevacizumab or osimertinib monotherapy in previously untreated patients with advanced EGFR-positive non-squamous NSCLC. METHODSWe previously reported the primary results of a randomized, open-label, phase II study comparing osimertinib plus bevacizumab with osimertinib monotherapy for this population. In this exploratory analysis using tissue and plasma samples, we evaluated gene profiles at baseline and disease progression or the last dose using targeted deep sequencing. RESULTSThe median progression-free survival (PFS) by the blinded independent central reviewer (BICR) were 22.1 months for the osimertinib plus bevacizumab arm and 20.2 months for the osimertinib arm (hazard ratio [HR], 0.864, 95% confidence interval [CI], 0.549–1.359). The 3-year overall survival was not different between the two arms (osimertinib plus bevacizumab: 57.1%; osimertinib monotherapy: 65.0%; HR, 95% CI, 0.727–2.233). Ninety-four patients had evaluable plasma samples at baseline and 40 had evaluable pretreatment tissue samples. EGFR mutations (76.6%) and TP53 mutations (44.7%) were detected in plasma samples at baseline. In patients with plasma TP53 mutations (N = 42), the median PFS by BICR was 19.8 months for the osimertinib plus bevacizumab arm and 20.2 months for the osimertinib arm (HR, 1.107, 95% CI, 0.534–2.297). CONCLUSIONSThere was also no significant difference in the PFS between the two arms, even in patients with TP53 mutations.