WCLC 2025 - Posters & ePosters-P3.12.64 Frontline Treatment Duration in MET-Amplified NSCLC After Third-Generation Egfr-TKI Failure: SACHI Study Insights

P3.12.64 Frontline Treatment Duration in MET-Amplified NSCLC After Third-Generation Egfr-TKI Failure: SACHI Study Insights

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This analysis from the phase 3 SACHI study provides insights into the characteristics and frontline treatment duration (DoT) of non-small cell lung cancer (NSCLC) patients with acquired MET amplification after progression on first-line (1L) third-generation (3rd-gen) EGFR tyrosine kinase inhibitors (TKIs). MET amplification is a key mechanism of acquired resistance to 3rd-gen EGFR-TKIs like osimertinib and is associated with shorter time to treatment failure (TTF) and poorer clinical outcomes.<br /><br />In SACHI, conducted in China, patients with MET gene copy number (GCN) ≥10 following prior 3rd-gen EGFR-TKI treatment were randomized to receive savolitinib plus osimertinib versus chemotherapy. Among 99 patients with MET GCN ≥10 (median age 59 years, 97% adenocarcinoma, ~44% had brain metastases), savolitinib plus osimertinib resulted in significantly longer progression-free survival (PFS) compared to chemotherapy (median PFS 6.9 vs 3.0 months; HR 0.32).<br /><br />Retrospective evaluation showed these patients had shorter median frontline DoT on 3rd-gen EGFR-TKIs (median 12.7 months, range 1–35.7) compared with historical data from the FLAURA study (median 16.2 months). For osimertinib specifically, the median DoT was 12.8 months in SACHI versus 16.2 months in FLAURA. This suggests that MET amplification accelerates disease progression and acts as an early resistance mechanism during prior EGFR-TKI therapy.<br /><br />The study highlights the aggressive nature of MET-amplified NSCLC after 3rd-gen EGFR-TKI failure and supports the therapeutic benefit of combining MET inhibitor savolitinib with osimertinib in this population. The findings underscore the importance of monitoring for MET amplification and adapting treatment strategies to overcome resistance. The study was funded by HUTCHMED and AstraZeneca and involved multiple cancer centers across China.<br /><br />In summary, MET amplification after frontline 3rd-gen EGFR-TKIs is associated with shorter treatment durations, indicating early resistance, but targeting MET alongside EGFR may improve patient outcomes.

Asset Subtitle

Lijuan Chen

Meta Tag

Speaker Lijuan Chen

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

MET amplification

non-small cell lung cancer

NSCLC

3rd-generation EGFR-TKIs

osimertinib

savolitinib

progression-free survival

treatment duration

acquired resistance

SACHI study