First-line MET tyrosine kinase inhibitors versus immunotherapy ± chemotherapy for patients with MET exon 14 skipping mutant metastatic NSCLC
Menée à partir de données portant sur 158 patients atteints d'un cancer du poumon non à petites cellules de stade métastatique et avec mutation du gène MET (perte de l’exon 14), cette étude identifie les facteurs liés à une utilisation, en traitement de première ligne, d'inhibiteurs de MET ou d'inhibiteurs de point de contrôle immunitaire avec ou sans chimiothérapie puis compare l'efficacité de ces deux stratégies du point de vue de la survie sans progression et de la survie globale
Purpose: First-line treatment options for MET exon 14 skipping (METex14) mutant metastatic non-small cell lung cancer (NSCLC) vary due to differences in drug approvals and clinical experience. This study investigates factors influencing outcomes with first-line MET tyrosine kinase inhibitors (TKI) versus immune checkpoint inhibitors (ICI)±chemotherapy.
Experimental Design: Clinicopathologic data were collected from patients with metastatic METex14 mutant NSCLC receiving first-line MET TKI or ICI±chemotherapy at five centers. Primary endpoints were real-world progression-free survival (rwPFS) and overall survival (OS) to first-line MET TKI versus ICI±chemotherapy. Subgroup analyses by clinicopathological characteristics were performed.
Results: Among 158 patients, 80 received MET TKI and 78 ICI±chemotherapy as first-line. Baseline clinicopathologic features were balanced except for higher proportion of patients with a history of smoking in the ICI±chemotherapy group (p=0.03). With a median follow-up of 37.9 months, no difference was observed in rwPFS (HR 0.85, p=0.4) or OS (HR 0.97, p=0.9) with first-line MET TKI versus ICI±chemotherapy. In subgroup analyses, first-line ICI±chemotherapy improved rwPFS in PD-L1≥80% (HR 0.50, p=0.03), while MET TKI improved rwPFS (HR 0.40, p=0.005) and OS (HR 0.49, p=0.03) in PD-L1<50%, as well as rwPFS (HR 0.39, p=0.02) and OS (HR 0.36, p=0.03) in brain metastases, and rwPFS in bone metastases (HR 0.55, p=0.01). No differences were observed in the incidence of high-grade toxicity (p=0.9) or rates of permanent discontinuation (p=0.2) between first-line MET TKI and ICI±chemotherapy.
Conclusions: First-line MET TKI improved outcomes in PD-L1<50% and brain/bone metastases, while ICI±chemotherapy prolonged PFS only in PD-L1≥80%, emphasizing the need for personalized treatment selection.
Clinical Cancer Research , résumé, 2025