PFS gains seen with savolitinib–osimertinib combo in EGFR-mutant, MET-amplified NSCLC

Treatment with the combination of savolitinib plus osimertinib prolongs progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC) harbouring EGFR mutation and MET amplification, as shown in the phase III SACHI trial.

SACHI included 211 Asian patients with locally advanced or metastatic EGFR mutation-positive NSCLC with MET amplification who progressed on EGFR tyrosine kinase inhibitor (TKI) therapy, of which 137 (65 percent) were naïve to third-generation EGFR TKI.

The patients were randomly assigned to receive treatment with once-daily oral savolitinib plus osimertinib (n=106; median age 59.4 years, 58 percent female) or intravenous chemotherapy (pemetrexed plus either cisplatin or carboplatin; n=105; median age 61.9 years, 52 percent female), both in 21-day cycles.  

The primary endpoint of investigator-assessed PFS was significantly longer with savolitinib–osimertinib vs chemotherapy in the subgroup of third-generation EGFR TKI-naïve patients (9.8 vs 5.4 months; hazard ratio [HR], 0.34, 95 percent confidence interval [CI], 0.21–0.56; p<0.0001) and in the overall population (8.2 vs 4.5 months; HR, 0.34, 95 percent CI, 0.23–0.49; p<0.0001).

In terms of safety, grade 3 or worse treatment-emergent adverse events occurred in 57 percent of patients each in the combination and chemotherapy groups.

The findings highlight this combination regimen as a potential oral treatment option for this biomarker-selected population.