Osimertinib + savolitinib sets a new standard of care for EGFR-mutated lung cancer

Two landmark phase 3 trials presented at the 2026 ESMO Congress are rewriting the playbook for EGFR-mutated NSCLC. The global SAFFRON trial showed that the all-oral combination of osimertinib (Tagrisso) plus the MET inhibitor savolitinib (Orpathys) significantly outperformed platinum/pemetrexed chemotherapy in patients whose disease progressed on osimertinib and had MET overexpression and/or amplification — a resistance mechanism seen in roughly one-third of patients. Experts at the meeting declared it "a new global standard of care." Regulatory filings are now under review by the FDA, the European Medicines Agency, and Japan's Ministry of Health.

The China-based SANOVO trial took things a step further, testing the combination in the first-line setting. In patients with MET IHC 3+ disease, adding savolitinib to frontline osimertinib more than doubled median progression-free survival compared to osimertinib alone, with an early OS signal also favoring the doublet. Both trials underscore the growing importance of comprehensive MET testing — by both IHC and FISH — at diagnosis and at disease progression.

By the Numbers:

• SAFFRON: Median PFS 7.6 vs. 5.4 months (HR 0.55; P < .001); Median OS 17.8 vs. 12.9 months (HR 0.68; P = .010)
• SAFFRON: 12-month OS rate 70% vs. 53%; confirmed ORR 51% vs. 27%
• SANOVO (MET IHC 3+): Median PFS 24.8 vs. 11.1 months (HR 0.45; P < .0001)
• SANOVO (ITT): Median OS 44.5 vs. 34.9 months (HR 0.48); 3-year OS 67.4% vs. 47.4%

Why it matters: These trials establish dual EGFR/MET blockade as an effective, biomarker-directed, all-oral strategy — both after osimertinib resistance and potentially in the first line — offering patients a chemotherapy-free option and clinicians a clearer roadmap for sequencing therapies in EGFR-mutated NSCLC.