A chemo-free second-line option for MET-amplified NSCLC

In the phase 3 SACHI study, the combination of savolitinib and osimertinib demonstrated clinically meaningful improvements in progression-free survival (PFS) and response rates, compared with chemotherapy, in participants with EGFR-mutant non-small cell lung cancer (NSCLC) who had progressed on first-line EGFR tyrosine kinase inhibitors (TKI).

Acquired MET amplification is a key resistance mechanism in pretreated EGFR-mutant NSCLC and is associated with poor prognosis. Savolitinib is a highly selective, oral MET TKI that has shown encouraging activity in combination with osimertinib in both phase 1 and 2 trials [1,2]. To further evaluate this combination, the phase 3 SACHI study (NCT05015608) compared its efficacy and safety with standard platinum-based doublet chemotherapy in participants with locally advanced or metastatic EGFR-mutant NSCLC and acquired MET amplification following progression on first-line EGFR TKI therapy.

The SACHI trial randomised 211 participants 1:1 to receive either savolitinib plus osimertinib or platinum-based chemotherapy until disease progression or intolerable toxicity. Cross-over to the combination therapy was permitted for participants in the chemotherapy arm upon progression. “At the data cut-off, 43% of participants initially assigned to chemotherapy had crossed over to receive the combination,” reported Dr Shun Lu (Shanghai Chest Hospital, China) [3].

Median PFS, the study’s primary endpoint, was significantly longer in the combination arm compared with chemotherapy: 7.2 months versus 4.2 months, corresponding to a hazard ratio (HR) of 0.40 (95% CI 0.28–0.59; P<0.0001). This benefit was consistent across all pre-specified subgroups, including age, sex, smoking status, prior use of third-generation EGFR TKI, EGFR mutation subtype, and metastatic burden or location.

The objective response rate was higher in the savolitinib-osimertinib arm than in the chemotherapy arm (58% vs 34%). Disease control rate also favoured the combination (89% vs 67%), as did median duration of response (8.4 vs 3.2 months). Longer follow-up is needed to fully assess overall survival outcomes. Grade 3 or higher adverse events occurred at similar rates in both arms (57% vs 57%), indicating comparable safety.

Dr Lu concluded: “The savolitinib-osimertinib combination may offer a new chemotherapy-free treatment option for patients with EGFR-mutated NSCLC and acquired MET amplification following progression on first-line therapy.”

1. Hartmaier RJ, et al. Cancer Discover. 2023;13;98-113.
2. Ahn M-J, et al. J Thorac Oncol. 2025;20:S4-5.
3. Lu S, et al. Savolitinib combined with osimertinib versus chemotherapy in EGFR-mutant and MET-amplification advanced NSCLC after disease progression on EGFR tyrosine kinase inhibitor: Results from a randomized phase 3 SACHI study. LBA8505, ASCO Annual Meeting 2025, 30 May–3 June, Chicago, IL, USA.

Medical writing support was provided by Dr Marten Dooper.
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Posted on 5 June 20255 June 2025