Real-world insights into patients with advanced NSCLC and MET alterations. (September 2021)

• Record Type: Journal Article
• Authors: Bittoni, Marisa; Yang, James Chih-Hsin; Shih, Jin-Yuan; Peled, Nir; Smit, Egbert F.; Camidge, D. Ross; Arasada, Rajeswara Rao; Oksen, Dina; Boutmy, Emmanuelle; Stroh, Christopher; Johne, Andreas; Carbone, David P.; Paik, Paul K.
• Is Part Of: Lung cancer. Volume 159(2021)
• Page Start: 96
• Page End: 106
• Publication Date: 2021-09
• Subjects: ALK anaplastic lymphoma kinase -- BMI body mass index -- BOR best overall response -- BRAF B-Raf proto-oncogene -- CDK6 cell division protein kinase 6 -- CI confidence interval -- CR complete response -- DoR duration of response -- ECOG PS Eastern Cooperative Oncology Group Performance Status -- EGFR epidermal growth factor receptor -- EMR electronic medical record -- FISH fluorescence in situ hybridization -- GCN gene copy number -- HGF hepatocyte growth factor -- ICI immune checkpoint inhibitor -- KRAS Kirsten Rat Sarcoma virus -- MET mesenchymal epithelial transition factor -- METex14 MET exon 14 -- NA not available -- NE not estimable -- NGS next-generation sequencing -- NSCLC non-small cell lung cancer -- ORR overall response rate -- OS overall survival -- PD progressive disease -- PD-L1 programmed death-ligand 1 -- PFS progression-free survival -- PR partial response -- RECIST Response Evaluation Criteria In Solid Tumors -- ROS reactive oxygen species -- SD stable disease -- TNTD time to next treatment or death -- USA United States of America; Advanced NSCLC -- MET exon 14 -- MET amplification -- Treatment patterns -- Real-world data -- Outcomes -- Biomarkers; Systemic treatments; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2021.06.015
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Patients with MET ex14 and MET amplified NSCLC differ in characteristics. Patients with MET ex14 skipping NSCLC rarely had concomitant driver alterations. Treatment patterns were heterogeneous; non-targeted treatments are commonly used. Real-world outcomes indicate that these patients have a high unmet medical need. Testing for MET alterations to identify patients that may benefit from targeted therapy is needed. Abstract: Objectives: To describe characteristics, treatment and outcomes of non-small cell lung cancer (NSCLC) patients with MET alterations ( MET exon 14 [ MET ex14] skipping or MET amplification [ MET amp]) in real-world clinical care. Methods: This non-interventional cohort study used real-world data extracted from electronic medical records from academic oncology sites in Israel, The Netherlands, Taiwan, and the USA. Patients had confirmed diagnosis of advanced (Stage IIIB–IV) NSCLC harboring MET alterations (date of diagnosis = index date) between 1 Jan 2010 and 30 Sept 2018. Medical history was assessed prior to and at the index date (baseline period), and outcomes from first date of treatment to death, loss to follow-up, or end of study period. Results: A total of 117 patients were included ( MET ex14 n = 70; MET amp n = 47); testing methods were heterogeneous. Concomitant oncogenic mutations were more common in the MET amp cohort than MET ex14. Patients in the MET ex14 cohort were older than those in MET amp, and a larger proportion were never smokers. Anticancer first-line therapies received by patients ( MET ex14; MET amp) included chemotherapy only (44%; 41%), MET inhibitors (33%; 29%), immune checkpoint inhibitor (ICI) mono-(12%; 15%) and combination-therapy (8%; 3%). Second-line therapies included chemotherapy (35%; 30%) and MET inhibitors (30%; 39%). In the MET ex14 cohort, objective response rate (ORR) was generally low (first-line 28%; second-line 30%); no patients who received ICIs had a response. In the MET amp cohort, ORR was 36% in first-line and 22% in second-line. Median (95% confidence interval) overall survival from start of first-line therapy was 12.0 months (6.8, 19.2) in the MET ex14 cohort and 22.0 months (9.8, 31.2) in MET amp. Conclusions: Heterogeneous treatments reflect the changing landscape and availability of new treatments, as well as the high unmet medical need in older, MET ex14 patients who had more advanced disease at diagnosis. MET-targeted therapies could be beneficial in patients with these rare MET alterations.