Final OS results and subgroup analysis of savolitinib in patients with MET exon 14 skipping mutations (METex14+) NSCLC

Savolitinib, a highly selective MET tyrosine kinase inhibitor, has shown promising activity and tolerable safety in patients (pts) with pulmonary sarcomatoid carcinoma (PSC) and other NSCLCs harboring MET exon14 skipping mutations (METex14+) (Lu, 2021). Here we report the long-term overall survival (OS), exposure and subgroup analysis results. In the open-label phase 2 study, eligible pts received oral savolitinib at 600 mg (body weight ≥50 kg) or 400 mg (<50 kg), QD in 21-day cycles. The primary objectives were OS and treatment exposure with a longer follow up time. Subgroup analysis was performed by prior systemic treatment (yes vs. no), NSCLC subtypes (PSC vs. other NSCLCs) and brain metastases. Of 70 pts enrolled and assigned to treatment (FAS), 25 were diagnosed as PSC and 45 as other NSCLCs, 28 were treatment-naïve and 42 were pretreated, 15 pts had CNS lesions. The data cutoff for final analysis was Jun 28, 2021. Eight pts are still on-treatment and 14 (20%) pts with more than 18-mo treatment. With a median follow up time of 28.4 mo (IQR 26.2–36.3), the median OS (mOS) was 12.5 mo (95%CI 10.5–21.4) in FAS; 18-mo OS rate, 42.1%; 24-mo OS rate, 31.5%. In pretreated and treatment naïve subgroups, 28.6% (12/42) and 46.4% (13/28) were PSC pts, respectively, and mOS was 19.4 mo (95%CI 10.5-31.3) and 10.9 mo (95%CI 7.5–14.0); 18-mo OS rate, 50.4% and 29.7%; 24-mo OS rate, 37.5% and 22.3%; respectively. In PSC and other NSCLC pts, mOS was 10.6 mo (95%CI 4.6–14.0) and 17.3 mo (95%CI 10.6–23.6); 18-mo OS rate, 29.9% and 49.0%; 24-mo OS rate, 25.6% and 34.7%; respectively. Pts with brain metastases had mOS of 17.7 mo (95%CI 10.48–NA), 18-m OS rate 50.0% and 24-m OS rate 35.7%. Grade ≥3 treatment-related adverse events were reported in 32 (45.7%) pts, the most frequent being AST increased (12.9%), ALT increased (10.0%) and peripheral oedema (8.6%). Overall, with prolonged follow-up and exposure, the incidences of AE were similar to previously reported data, and consistent across subgroups. The updated results further confirm the favorable benefit of savolitinib in pts with METex14+ NSCLC and each subgroup, and the acceptable safety profile.