Clinical outcomes of tepotinib and immune checkpoint inhibitor therapy for MET exon 14 skipping NSCLC: A multicentric retrospective analysis.

Abstract

8631 Background: The VISION study demonstrated that tepotinib, a MET inhibitor, is effective against MET exon 14 (METex14) skipping NSCLC, but the clinical data on the efficacy and safety of this drug are scarce, and the utility of immune checkpoint inhibitors (ICIs) in patients with METex14 requires further investigation. The present, multicentric, retrospective study evaluated the clinical efficacy and safety of tepotinib and ICIs in patients with METex14 skipping NSCLC. Methods: Data on the patient characteristics, treatment details, efficacy, and safety of tepotinib and ICIs in patients with METex14 skipping NSCLC diagnosed at any of six Japanese hospitals between August 2020 and December 2024 were extracted from electronic medical records and retrospectively analyzed. Results: Of the 98 patients enrolled, 57 (58.2%) and 41 (41.8%) were male and female, respectively. 60 patients (61.2%) had a smoking history. Histological data indicated adenocarcinoma in most of the patients (68.4%). There were 50 patients (51.0%) with PD-L1 > 50%. Tepotinib was administered to 79 patients with a median age of 75 years (range: 55–90 years). Most of these patients had advanced-stage cancer. Tepotinib was administered as the first-line therapy in 62 patients (78.5%), with 19.0, 55.7, 17.7, 6.3, and 1.3% of this subgroup having ECOG PS 0, 1, 2, 3, and 4, respectively. The median observation period was 29.1 months (range: 1.5–51.5 months). First-line tepotinib therapy achieved a 61.4% overall response rate (ORR; 95% confidence interval [CI]: 48.8–74.0), median progression-free survival (PFS) of 8.2 months (95% CI: 6.3–10.1), and median overall survival (OS) of 24.4 months (95% CI: 9.5–39.2). The most common adverse event (AE) was edema (71.0%), with Grade 3 or higher edema occurring in 12.9% of the patients. Notably, these patients had significantly longer PFS than those without edema (10.8 months [95% CI: 8.0–13.6] vs. 4.2 months [95% CI: 2.8–5.5]; hazard ratio: 0.31; 95% CI: 0.16 to 0.60; P < 0.001). Treatment-related AEs led to tepotinib discontinuation in 15.0% of the cohort, and dose interruption and dose reduction were required in 59.5% and 62.0% of the cohort, respectively. ICI therapy, which was administered to 34 patients at various times, achieved a median PFS of 28.8 months (95% CI: 9.3–52.5) and a median OS of 45.2 months (95% CI: 20.9–77.0). Conclusions: The present, real-world analysis corroborated the findings of the VISION study demonstrating the efficacy and safety of tepotinib therapy against METex14 skipping NSCLC. The association between tepotinib-related edema and longer PFS warrants further investigation. Importantly, ICIs appear to be a promising treatment option for this population and deserve further study.