Multicenter phase 3 trial of savolitinib plus osimertinib versus chemotherapy for advanced, EGFR mutation-positive, MET-amplified NSCLC

Savolitinib combined with osimertinib is a potential novel oral therapy for patients with EGFR mutation-positive non-small cell lung cancer (NSCLC) harboring MET amplification after progression on EGFR TKI therapy. The phase 3 SACHI trial, at 68 centers in China, evaluated this combination versus standard of care platinum-based doublet chemotherapy in this patient population. Patients were randomized to savolitinib plus osimertinib (n=106) of chemotherapy (n=105), with 69 and 68 third-generation EGFR TKI-naïve patients in the savolitinib-osimertinib group and the chemotherapy group, respectively. Median progression-free survival was significantly improved with savolitinib-osimertinib versus chemotherapy in the third-generation EGFR TKI-naïve population (9.8 versus 5.4 months; HR 0.34; p<0.0001) and in the ITT population (8.2 versus 4.5 months; HR 0.34; pxtagstartz0.0001). Grade 3 or worse treatment-emergent adverse events occurred in the same proportion of patients in both groups (57% and 57%). The authors conclude that savolitinib-osimertinib improved PFS versus chemotherapy in patients with EGFR mutation-positive,