Asian Thoracic Oncology Research Group (ATORG) Expert Consensus Statement on MET Alterations in NSCLC: Diagnostic and Therapeutic Considerations

• Published in: Clinical lung cancer Vol. 23; no. 8; pp. 670 - 685
• Main Authors: Ahn, Myung-Ju, Mendoza, Marvin Jonne L., Pavlakis, Nick, Kato, Terufumi, Soo, Ross A., Kim, Dong-Wan, Liam, Chong Kin, Hsia, Te-Chun, Lee, Chee Khoon, Reungwetwattana, Thanyanan, Geater, Sarayut, Chan, Oscar Siu Hong, Prasongsook, Naiyarat, Solomon, Benjamin J., Nguyen, Thi Thai Hoa, Kozuki, Toshiyuki, Yang, James Chih-Hsin, Wu, Yi-Long, Mok, Tony Shu Kam, Tan, Daniel Shao-Weng, Yatabe, Yasushi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2022
• Subjects: Asia-Pacific; Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Drug Resistance, Neoplasm - genetics; Epithelial-Mesenchymal Transition; ErbB Receptors - genetics; Humans; Lung cancer; Lung Neoplasms - diagnosis; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; MET amplification in EGFR TKI resistance; MET exon 14 mutation; MET inhibitors; Mutation; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Proto-Oncogene Proteins c-met; ALK; ASCO; MET exon 14 mutation; MET amplification in EGFR TKI resistance; MET inhibitors; IHC; TRAE; Lung cancer; DoR; mDoR; ALT; CNS; ATORG; M; ctDNA; EGFR; ORR; APAC; Asia-Pacific; mOS; QD; ECOG; RT-PCR; PD-L1; BID; PFS; ctRNA; AST; mPFS; AE; NSCLC; OS; SOC; ErbB3; MET ex14; TMB; CGP; GCN; TKI; CDx; FISH; KRAS; NGS; MET; PCR; c-MET/MET
• ISSN: 1525-7304; 1938-0690
• DOI: 10.1016/j.cllc.2022.07.012

•MET alterations are associated with tumorigenesis and TKI resistance in patients with non-small cell lung cancer (NSCLC)•ATORG provides recommendations for diagnosis of (Mesenchymal Epithelial Transition) MET alterations in NSCLC•ATORG recommends MET exon 14 testing within panels for driver mutations in NSCLC•MET inhibitors can be considered for first or subsequent lines of treatment•Enrolment of patients is encouraged in combination trials of tyrosine kinase inhibitors (TKIs) and MET inhibitors Non-small cell lung cancer (NSCLC) is a heterogeneous disease, with many oncogenic driver mutations, including de novo mutations in the Mesenchymal Epithelial Transition (MET) gene (specifically in Exon 14 [ex14]), that lead to tumourigenesis. Acquired alterations in the MET gene, specifically MET amplification is also associated with the development of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in patients with EGFR-mutant NSCLC. Although MET has become an actionable biomarker with the availability of MET-specific inhibitors in selected countries, there is differential accessibility to diagnostic platforms and targeted therapies across countries in Asia-Pacific (APAC). The Asian Thoracic Oncology Research Group (ATORG), an interdisciplinary group of experts from Australia, Hong Kong, Japan, Korea, Mainland China, Malaysia, the Philippines, Singapore, Taiwan, Thailand and Vietnam, discussed testing for MET alterations and considerations for using MET-specific inhibitors at a consensus meeting in January 2022, and in subsequent offline consultation. Consensus recommendations are provided by the ATORG group to address the unmet need for standardised approaches to diagnosing MET alterations in NSCLC and for using these therapies. MET inhibitors may be considered for first-line or second or subsequent lines of treatment for patients with advanced and metastatic NSCLC harbouring MET ex14 skipping mutations; MET ex14 testing is preferred within multi-gene panels for detecting targetable driver mutations in NSCLC. For patients with EGFR-mutant NSCLC and MET amplification leading to EGFR TKI resistance, enrolment in combination trials of EGFR TKIs and MET inhibitors is encouraged.