Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2025
Osimertinib Plus Savolitinib in Patients With EGFR-Mutated Advanced NSCLC With MET Alterations After First-Line Osimertinib: Clinical Outcomes, Safety, and Biomarker Analysis: A Brief Report.
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Le Xiuning, Baik Christina, Cho Byoung Chul, Riess Jonathan W, Piotrowska Zofia, Johannes de Langen Adrianus, Goldberg Sarah B, Goldman Jonathan W, Reguart Noemi, Shiraishi Yoshimasa, Ambrose Helen, Fraenkel Paula G, Ruiz Brayan Merchan, Smith Paul E, Tang Kwan Ho, Yu Helena A
Аннотация
INTRODUCTION: The ORCHARD (NCT03944772) study was conducted to characterize resistance mechanisms and identify optimal treatments after progressive disease (PD) on first-line osimertinib. We report results from the osimertinib plus savolitinib module.
METHODS: Patients with EGFR-mutated NSCLC with PD on first-line osimertinib with MET gene amplification (≥4 copies of MET over tumor ploidy) per next-generation sequencing of a post-progression biopsy received osimertinib plus savolitinib. Primary end point was investigator-assessed objective response rate (ORR). Secondary end points included progression-free survival, duration of response, overall survival, and safety. Correlation of ORR with baseline molecular alterations was an exploratory analysis.
RESULTS: A total of 32 patients were enrolled; all had tumors with MET amplification. At primary analysis cutoff (January 2023), confirmed ORR was 47% (80% confidence interval [CI]: 34-60). Median duration of response was 14.5 months (95% CI: 5.6-18.7). Median progression-free survival was 7.6 months (95% CI: 3.2-15.9). There was a trend toward increased ORR in patients with high MET gene copy number (≥10 versus <10). Furthermore, 14 patients (44%) had grade 3 or higher treatment-emergent adverse events; most often pneumonia (n = 3; 9%). At final database lock (May 2024), 20 patients (63%) had died; median overall survival was 20.7 months (95% CI: 9.9-34.8).
CONCLUSIONS: Osimertinib plus savolitinib demonstrated encouraging clinical benefit in patients with EGFR-mutated advanced NSCLC and MET amplification after PD on first-line osimertinib. Safety was consistent with profiles of the individual drugs.
METHODS: Patients with EGFR-mutated NSCLC with PD on first-line osimertinib with MET gene amplification (≥4 copies of MET over tumor ploidy) per next-generation sequencing of a post-progression biopsy received osimertinib plus savolitinib. Primary end point was investigator-assessed objective response rate (ORR). Secondary end points included progression-free survival, duration of response, overall survival, and safety. Correlation of ORR with baseline molecular alterations was an exploratory analysis.
RESULTS: A total of 32 patients were enrolled; all had tumors with MET amplification. At primary analysis cutoff (January 2023), confirmed ORR was 47% (80% confidence interval [CI]: 34-60). Median duration of response was 14.5 months (95% CI: 5.6-18.7). Median progression-free survival was 7.6 months (95% CI: 3.2-15.9). There was a trend toward increased ORR in patients with high MET gene copy number (≥10 versus <10). Furthermore, 14 patients (44%) had grade 3 or higher treatment-emergent adverse events; most often pneumonia (n = 3; 9%). At final database lock (May 2024), 20 patients (63%) had died; median overall survival was 20.7 months (95% CI: 9.9-34.8).
CONCLUSIONS: Osimertinib plus savolitinib demonstrated encouraging clinical benefit in patients with EGFR-mutated advanced NSCLC and MET amplification after PD on first-line osimertinib. Safety was consistent with profiles of the individual drugs.