Multicenter randomized phase 2 trial of first-line osimertinib with or without savolitinb for MET-aberrant, EGFR-mutant non-small cell lung cancer

The multicenter randomized FLOWERS trial in China evaluated first-line osimertinib with or without savolitinib for patients with advanced non-small cell lung cancer (NSCLC) with EGFR mutations and de novo MET aberrations. Treatment-naïve patients with locally advanced or metastatic NSCLC harboring de novo MET MET amplification or overexpression and EGFR mutations were randomized to receive osimertinib 80 mg orally once daily (cohort 1; n=23) or combination therapy (cohort 2; osimertinib 80 mg orally once daily plus savolitinib 300 mg orally twice daily; n=21). The primary endpoint was confirmed objective response rate (ORR). The confirmed ORR was 60.9% (95% CI 38.5-80.3) in cohort 1 and 90.5% (69.9-98.8) in cohort 2, with disease control rates of 87% (66.4-97.2) and 95.2% (76.2-99.9), respectively. Treatment-related adverse events of grade 3 or higher occurred in 2 patients (8.7%) in cohort 1 and 12 patients (57.1%) in cohort 2. The authors conclude that osimertinib plus savolitinib showed promising antitumor activity and manageable safety.