Case report on sequential therapy for MET exon 14 skipping NSCLC with high PD-L1

In the precision management of non-small cell lung cancer (NSCLC), identifying driver mutations and evaluating immune-related biomarkers are essential. Yet, clear therapeutic protocols remain absent for tumors that concurrently carry MET exon 14 skipping mutations (METex14) and demonstrate elevated programmed death ligand-1 (PD-L1) expression. This report details the case of a 79-year-old male with a prolonged smoking history who quit 20 years ago, diagnosed with left lung NSCLC. Pathological analysis revealed high PD-L1 expression in the tumor (tumor proportion score 99%), alongside a METex14 mutation. Initial therapy employed the PD-1 inhibitor Tislelizumab, yielding a progression-free survival (PFS) of 7 months. Treatment was then modified to the MET tyrosine kinase inhibitor (MET-TKI) Savolitinib, which led to marked tumor reduction. Following discontinuation of Savolitinib due to drug-induced liver injury, Tislelizumab, previously associated with resistance, was reintroduced as a “rechallenge” successfully re-establishing disease control. This distinctive therapeutic sequence provides clinical evidence that “MET inhibitors may counteract acquired resistance to PD-1 inhibitors”. Beyond underscoring the value of personalized treatment in the intricate setting of coexisting high PD-L1 expression and MET-driven mutations, this case hints at a novel strategy: sequential MET inhibitor treatment restore sensitivity to immunotherapy responses by modifying the tumor microenvironment. Coupled with a systematic review of pertinent literature, this article explores the clinical features, therapeutic challenges, potential resistance mechanisms, and management approaches for such patients. It also outlines future research avenues for combination or sequential therapies, aiming to furnish a more holistic reference for clinical decision-making.