MedicineEurope PMC
Ranked by formulaVerdict: MajorOsimertinib-Savolitinib in Advanced NSCLC after Progression during EGFR-TKI Therapy
Savolitinib is an oral, potent, highly selective MET-tyrosine kinase inhibitor (TKI).
Key numbers
- 90% of tumor cells on
- 95% confidence interval
- 95% CI
VerdictA leading story on any desk.
Abstract
Background Savolitinib is an oral, potent, highly selective MET-tyrosine kinase inhibitor (TKI). Combination therapy with savolitinib and osimertinib, an epidermal growth factor receptor (EGFR)-TKI, has shown activity in patients with EGFR-mutated, advanced non-small-cell lung cancer (NSCLC) with MET overexpression, MET amplification, or both, after progression during EGFR-TKI therapy. Methods In this international, phase 3, open-label trial, we randomly assigned, in a 1:1 ratio, patients with EGFR-mutated, locally advanced or metastatic NSCLC with MET overexpression (staining intensity of 3+ for MET in ≥90% of tumor cells on immunohistochemical analysis), MET amplification (≥10 gene copies on fluorescence in situ hybridization), or both whose disease had progressed during osimertinib therapy to receive osimertinib (at a dose of 80 mg once daily) plus savolitinib (300 mg twice daily) or intravenous platinum-pemetrexed. The primary end point was progression-free survival, as assessed by blinded independent central review. Secondary end points included overall survival and safety. Results Of the 1746 patients screened, 338 were randomly assigned to receive osimertinib-savolitinib (171 patients) or platinum-pemetrexed (167 patients). Osimertinib-savolitinib led to significantly longer progression-free survival than platinum-pemetrexed (hazard ratio for disease progression or death, 0.55; 95% confidence interval [CI], 0.42 to 0.72; P<0.001), as well as significantly longer overall survival (hazard ratio for death, 0.68; 95% CI, 0.50 to 0.91; P = 0.01; final analysis). The Kaplan-Meier estimate of 12-month progression-free survival was 36% in the osimertinib-savolitinib group and 10% in the platinum-pemetrexed group, and the estimate of 12-month overall survival was 70% and 53%, respectively. The most frequently reported adverse events that occurred during treatment in the osimertinib-savolitinib group were peripheral edema (in 49% of the patients), anemia (in 26%), and diarrhea (in 26%). Grade 3 or higher adverse events during treatment were reported in 64% of the patients in the osimertinib-savolitinib group and in 63% of those in the platinum-pemetrexed group. Conclusions Osimertinib-savolitinib led to significantly longer progression-free and overall survival than platinum-pemetrexed among patients with EGFR-mutated, locally advanced or metastatic NSCLC with MET overexpression, MET amplification, or both that had progressed during osimertinib therapy (Funded by AstraZeneca; SAFFRON ClinicalTrials.gov number, NCT05261399.).
The editor's rubric
- Leverage2 / 5
- Reusable within one subfield (a technique, dataset, or protocol a few groups will adopt).
- Magnitude3 / 5
- Large gain: roughly 2x, or a clear new state of the art on a hard, unsaturated problem.
- Evidence5 / 5
- Definitive: phase 3 randomized evidence on hard endpoints, multi-lab replication, or community verification at scale.
- Novelty3 / 5
- A genuinely new approach to an open problem.
- Trajectory2 / 5
- Some room to improve with obvious engineering.
- Stakes3 / 5
- Meaningful benefit to many people within a few years.
Editor’s rationale
Heuristic triage from title and abstract text only, not a reading of the paper. Cues found: gains (efficacy); design (randomized, blinded, phase 3); verification (confidence interval, p-value); stakes (mortality, major disease, prevention or cure).
How the score was computed
Desks place stronger verdicts first, then use this score to order work within the same verdict.
- Merit
- 7.0 / 10
- Adjusted merit
- 5.5 / 10
- Attention
- 0%
- Freshness
- 85%
- Citations0 (reference 20, via openalex, Oct 27, 2026, 06:17 UTC)