NSCLC patients with MET non-exon-14 mutations rather than MET exon 14 mutations response to immune checkpoint inhibitors

MET is a well-known oncogene, and various MET mutations accompanying MET pathway dysregulation have been reported in several solid tumors [ [1] Guo R. Luo J. Chang J. Rekhtman N. Arcila M. Drilon A. MET-dependent solid tumours - molecular diagnosis and targeted therapy. Nat. Rev. Clin. Oncol. 2020; 17: 569-587 Crossref PubMed Scopus (100) Google Scholar ]. In the article published by Mayenga et al., they described that 46.2 % of MET exon 14 (METex14) mutant non-small-cell lung cancer (NSCLC) patients (6/13) could obtain durable responses to immune checkpoint inhibitors (ICIs) treatment [ [2] Mayenga M. Assié J.B. Monnet I. Massiani M.A. Tabeze L. Friard S. Fraboulet S. Métivier A.C. Chouaïd C. Zemoura L. Longchampt E. Callens C. Melaabi S. Couderc L.J. Doubre H. Durable responses to immunotherapy of non-small cell lung cancers harboring MET exon-14-skipping mutation: A series of 6 cases. Lung Cancer. 2020; 150: 21-25 Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar ]. And they suggested that ICIs could be considered an option to treat NSCLC patients with METex14 mutations. These findings by Mayenga et al. are concordant with our previous study focusing on MET mutations and ICIs [ [3] Li X. Wang R. Wang L. MET-mutant cancer and immune checkpoint inhibitors: a large database analysis. Lung Cancer. 2020; 150: 256-258 Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar ], but are contradictory to other studies focusing on METex14 mutations in NSCLC [ [4] Sabari J.K. Leonardi G.C. Shu C.A. Umeton R. Montecalvo J. Ni A. Chen R. Dienstag J. Mrad C. Bergagnini I. Lai W.V. Offin M. Arbour K.C. Plodkowski A.J. Halpenny D.F. Paik P.K. Li B.T. Riely G.J. Kris M.G. Rudin C.M. Sholl L.M. Nishino M. Hellmann M.D. Rekhtman N. Awad M.M. Drilon A. PD-L1 expression, tumor mutational burden, and response to immunotherapy in patients with MET exon 14 altered lung cancers. Ann. Oncol. 2018; 29: 2085-2091 Abstract Full Text Full Text PDF PubMed Scopus (160) Google Scholar , [5] Kron A. Heydt C. Ruge L. Schaepers C. Eisert A. Merkelbach-Bruse S. Riedel R. Nogova L. Fischer R.N. Michels S. Abdulla D.S.Y. Koleczko S. Fassunke J. Schultheis A.M. Kron F. Ueckeroth F. Wessling G. Sueptitz J. Beckers F. Braess J. Panse J. Grohé C. Hamm M. Kabitz H.-J. Kambartel K. Kaminsky B. Krueger S. Schulte C. Lorenz J. Lorenzen J. Meister W. Meyer A. Kappes J. Reinmuth N. Schaaf B. Schulte W. Serke M. Buettner R. Wolf J. Genetic heterogeneity of MET-aberrant non-small cell lung cancer and its impact on the outcome of immunotherapy. J. Thorac. Oncol. 2020; Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar ]. Thus, there is a need to identify which MET mutation subtypes could benefit from ICIs, so much so that we can further improve survival outcomes of NSCLC patients.