Dr Schneider on Targeted Treatment Options in MET Exon 14 Mutated–NSCLC

Bryan Schneider, MD, clinical professor, service chief, Department of Internal Medicine, Division of Hematology/Oncology, associate medical director, Office of Research, service chief member, Rogel Cancer Center, University of Michigan Health, discusses agents available for use in the targeting of MET exon 14 mutations in non–small cell lung cancer (NSCLC).

MET exon 14 mutations are considered a rare oncogenic driver mutation, occurring in approximately 3% of patients with NSCLC, Schneider begins. These mutations result in the skipping of exon 14 during protein translation, leading to stage-dependent MET genomic amplification and c-MET overexpression that drives the oncogenic process, Schneider explains.

The MET-targeted kinase inhibitors capmatinib (Tabrecta) and tepotinib (Tepmetko) are both approved for this indication, Schneider continues. Tepotinib was granted accelerated approval by the FDA in February, 2021, based on efficacy data from the phase 2 VISION trial (NCT02864992). The agent produced an overall response rate (ORR) of 46.7% in the cohort of patients with MET exon 14 skipping alterations. Response rates were slightly higher in those who were given the first line treatment (50.7%) compared with those treated in the second line (43.4%).

Similarly, the FDA granted regular approval to capmatinib for patients with metastatic NSCLC harboring MET exon 14 skipping mutations in August of 2022, Schneider continues. The agent had been previously granted accelerated approval for this indication in 2020 based on initial efficacy data from the phase 2 GEOMETRY mono-1 trial (NCT02414139). In this trial, capmatinib produced response rates approaching 70% when used in the front line, and 41% in the second or third-line setting.

Importantly, the efficacy of these drugs remains consistent regardless of if the genomic alteration was identified through tissue sampling or plasma DNA analysis, Schneider notes. Accordingly, these 2 drugs are now favored when considering front line treatment options for these patients after initial detection of a MET exon 14 mutation, Schneider concludes.