The Efficacy and Safety of Treating Acquired MET Resistance Through Combinations of Parent and MET Tyrosine Kinase Inhibitors in Patients With Metastatic Oncogene-Driven NSCLC

作者：Tejas Patil, Alyse Staley, Yunan Nie, M Sakamoto, Margaret Stalker, James Jurica, Kenna Koehler, Amanda Cass, Halle Kuykendall, Emily E. Schmitt, Emma Filar, Evelina Reventaite, Kurt D. Davies, Hala Nijmeh, Mary Haag, Benjamin A. Yoder, Paul A. Bunn, Erin L. Schenk, Dara L. Aisner, Wade T. Iams, Melina E. Marmarelis, D. Ross Camidge · 发表于：JTO Clinical and Research Reports · 年份：2024 · DOI：10.1016/j.jtocrr.2024.100637 · 被引用次数：8 · 研究领域：Lung Cancer Treatments and Mutations、Lung Cancer Diagnosis and Treatment、Fibroblast Growth Factor Research

Acquired MET gene amplification, MET exon 14 skip mutations, or MET fusions can emerge as resistance mechanisms to tyrosine kinase inhibitors (TKIs) in patients with lung cancer. The efficacy and safety of combining MET TKIs (such as crizotinib, capmatinib or tepotinib) with parent TKIs to target acquired MET resistance is not well characterized. Multi-institutional retrospective chart review identified 83 patients with metastatic oncogene-driven NSCLC that were separated into two pairwise matched cohorts: (1) MET cohort (n = 41) – patients with acquired MET resistance continuing their parent TKI with a MET TKI added or (2) Chemotherapy cohort (n = 42) – patients without any actionable resistance continuing their parent TKI with a platinum pemetrexed added. Clinicopathologic features, radiographic response (via RECIST 1.1), survival outcomes, adverse events (via CTCAE 5.0) and genomic data were collected. Survival outcomes were assessed using Kaplan Meier methods. Multivariate modeling adjusted for lines of therapy, brain metastases, TP53 mutations, and oligometastatic disease. Within the MET cohort, median age was 56 years (range, 36–83 years). Most patients were never smokers (28/41, 68.3%). Baseline brain metastases were common (21/41, 51%). The most common oncogenes in the MET cohort were EGFR (30/41, 73.2%), ALK (7/41, 17.1%), and ROS1 (2/41, 4.9%). Co-occurring TP53 mutations (32/41, 78%) were frequent. Acquired MET alterations included MET gene amplification (37/41, 90...