WCLC 2025 - Posters & ePosters-P3.12.09 Efficacy of Tepotinib Against Non-Adenocarcinoma MET Exon 14 Skipping NSCLC: A Subanalysis of the REAL-MET Study

P3.12.09 Efficacy of Tepotinib Against Non-Adenocarcinoma MET Exon 14 Skipping NSCLC: A Subanalysis of the REAL-MET Study

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This retrospective, multicenter subanalysis of the REAL-MET study evaluated the efficacy and safety of tepotinib, a MET inhibitor, in patients with non-small cell lung cancer (NSCLC) harboring MET exon 14 (METex14) skipping alterations, focusing on non-adenocarcinoma histologies such as squamous cell carcinoma and sarcomatoid carcinoma. METex14 skipping drives oncogenesis in approximately 3% of NSCLC cases, predominantly adenocarcinomas (~79%). While prior studies (e.g., VISION) showed tepotinib’s benefit in METex14 skipping NSCLC primarily with adenocarcinoma histology, the drug’s impact on less common histologies remained unclear.<br /><br />The study enrolled 79 patients from six Japanese centers between 2020 and 2024, with 71% adenocarcinoma and 29% non-adenocarcinoma (including squamous cell carcinoma 10.1%, sarcomatoid 6.3%, and adenosquamous carcinoma 5.1%). Efficacy outcomes assessed included overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment toxicity.<br /><br />Results revealed that tepotinib had a significantly higher ORR and DCR in adenocarcinoma patients compared to non-adenocarcinoma (ORR 70.6% vs. 40.9%, p=0.021; DCR 96.1% vs. 77.3%, p=0.023). Although median PFS and OS favored adenocarcinoma patients, differences were not statistically significant. Importantly, tepotinib showed clinical efficacy and an acceptable safety profile in non-adenocarcinoma subgroups, suggesting meaningful benefit beyond the most common histology.<br /><br />In conclusion, this real-world study highlights that while tepotinib outcomes are superior in adenocarcinoma METex14 NSCLC, the drug remains an effective treatment option in patients with rarer non-adenocarcinoma histologies harboring METex14 skipping variants. These findings support tepotinib’s broader clinical utility across diverse NSCLC histologies with METex14 alterations.

Asset Subtitle

Ryota Saito

Meta Tag

Speaker Ryota Saito

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

tepotinib

MET exon 14 skipping

non-small cell lung cancer

NSCLC

adenocarcinoma

non-adenocarcinoma

squamous cell carcinoma

sarcomatoid carcinoma

overall response rate

progression-free survival