A randomised phase II study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations: the European Thoracic Oncology Platform (ETOP 10-16) BOOSTER trial

ABSTRACT Background While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small cell lung cancer (NSCLC) with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance. Patients and methods BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy. Primary endpoint was investigator assessed progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), and adverse events (AEs). Results Between 5/2017 and 2/2019, 155 patients were randomised (combination:78; osimertinib:77). At data cut-off of 22/02/2021, median follow-up was 33.8 months (m) (IQR:26.5-37.6) and 129 (83.2%) PFS events were reported in the ITT population. There was no difference in median PFS between combination (15.4m;95%CI:9.2-18.0) and osimertinib arm (12.3m;95%CI:6.2-17.2; stratified log-rank p=0.83), (HR=0.96; 95%CI:0.68-1.37). Median OS was 24.0m (95%CI:17.8-32.1) in the combination and 24.3m (95%CI:16.9-37.0) in the osimertinib arm (stratified log-rank p=0.91), (HR=1.03; 95%CI:0.67-1.56). Exploratory analysis revealed a significant interaction of smoking history with treatment for PFS (adjusted p=0.0052) with a HR of 0.52 (95%CI: 0.30-0.90) for smokers, and 1.47 (95%CI: 0.92-2.33) for never smokers. ORR was 55% in both arms and the median time to treatment failure was significantly shorter in the combination than in the osimertinib arm, 8.2m vs 10.8m, respectively (p=0.0074). Safety of osimertinib and bevacizumab was consistent with previous reports with grade≥3 treatment-related AEs (TRAEs) reported in 47% and 18% of patients on combination and osimertinib alone, respectively. Conclusions No difference in PFS was observed between osimertinib plus bevacizumab and osimertinib alone. Grade ≥3 TRAEs were more common in patients on combination.