Efficacy and Safety of Savolitinib Plus Osimertinib in EGFR-Mutant, MET-Aberrant Advanced Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVES: NSCLC is the leading cause of cancer-related mortality. While combined therapy including savolitinib and osimertinib appears promising, there exists a lack of comprehensive pooled evidence regarding its anti-oncological activity. UNLABELLED: The objective of this study is to evaluate the efficacy and safety of combined therapy in patients with NSCLC. METHODS: A comprehensive literature search was conducted in MEDLINE, the Cochrane Central Register of controlled trials, and ClinicalTrials.gov. Randomized controlled trials and prospective single-arm studies evaluating savolitinib combined with osimertinib were included. A random-effects single-arm meta-analysis of proportions was performed using logit transformation and inverse variance weighting, with restricted maximum likelihood (REML) estimation and Knapp-Hartung adjustment. Results were reported with a 95% CI, and heterogeneity was assessed using the I2 statistic. Sensitivity analysis was conducted using the Freeman-Tukey transformation. RESULTS: The primary analysis included 4 post-TKI, MET-selected combination cohorts (SACHI, SAVANNAH, and TATTON Part B; n=338) from 7 reports of 5 trials after de-duplication of overlapping data sets. First-line (FLOWERS) and MET-unselected (Yoh) cohorts were analyzed separately. The pooled objective response rate (ORR) was 53.9% (95% CI: 45.1-62.4), disease control rate (DCR) was 85.2% (79.2-89.8), 6-month progression-free survival (PFS) rate was 59.8%, and grade ≥3 adverse events occurred in 48.8% of patients. ORR estimates were consistent across studies and remained robust across sensitivity and subgroup analyses. CONCLUSIONS: Combined therapy shows encouraging results in selected MET, post-TKI NSCLC. However, reliance on single-arm data warrants further randomized controlled trials.