Uncommon Mutations in Non-Small Cell Lung Cancer (NSCLC): A Focus On MET



  1. Tabrectra. Prescribing information. Novartis Pharmaceuticals Corporation; 2022. Accessed January 9, 2023. https://www.novartis.com/us-en/sites/novartis_us/files/tabrecta.pdf
  2. Tepmetko. Prescribing information. EMD Serono; 2021. Accessed January 9, 2023. https://www.emdserono.com/us-en/pi/tepmetko-pi.pdf
  3. Pennell NA, Arcila ME, Gandara DR, West H. Biomarker testing for patients with advanced non-small cell lung cancer: real-world issues and tough choices. Am Soc Clin Oncol Educ Book. 2019;39:531-542. doi:10.1200/EDBK_237863
  4. Ferry-Galow KV, Datta V, Makhlouf HR, et al. What can be done to improve research biopsy quality in oncology clinical trials? J Oncol Pract. 2018;14(11):JOP1800092. doi:10.1200/JOP.18.00092
  5. NCCN. Clinical Guidelines in Oncology. Non–small cell lung cancer, version 1.2023. Accessed January 9, 2023. https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf
  6. Lee CC, Yamada KM. Identification of a novel type of alternative splicing of a tyrosine kinase receptor. Juxtamembrane deletion of the c-met protein kinase C serine phosphorylation regulatory site. J Biol Chem. 1994;269(30):19457-19461.
  7. Vuong HG, Ho ATN, Altibi AMA, Nakazawa T, Katoh R, Kondo T. Clinicopathological implications of MET exon 14 mutations in non-small cell lung cancer—A systematic review and meta-analysis. Lung Cancer. 2018;123:76-82. doi:10.1016/j.lungcan.2018.07.006
  8. Strickler JH, Weekes CD, Nemunaitis J, et al. First-in-human phase I, dose-escalation and -expansion study of telisotuzumab vedotin, an antibody-drug conjugate targeting c-Met, in patients with advanced solid tumors. J Clin Oncol. 2018;36(33):3298-3306. doi:10.1200/JCO.2018.78.7697
  9. Ma PC, Tretiakova MS, MacKinnon AC, et al. Expression and mutational analysis of MET in human solid cancers. Genes Chromosomes Cancer. 2008;47(12):1025-1037. doi:10.1002/gcc.20604
  10. Gu FF, Zhang Y, Liu YY, et al. Lung adenocarcinoma harboring concomitant SPTBN1-ALK fusion, c-Met overexpression, and HER-2 amplification with inherent resistance to crizotinib, chemotherapy, and radiotherapy. J Hematol Oncol. 2016;9(1):66. doi:10.1186/s13045-016-0296-8
  11. Singal G, Miller PG, Agarwala V, et al. Association of patient characteristics and tumor genomics with clinical outcomes among patients with non-small cell lung cancer using a clinicogenomic database. JAMA. 2019;321(14):1391-1399. doi:10.1001/jama.2019.3241
  12. Awad MM, Leonardi GC, Kravets S, et al. Impact of MET inhibitors on survival among patients with non-small cell lung cancer harboring MET exon 14 mutations: a retrospective analysis. Lung Cancer. 2019;133:96-102. doi:10.1016/j.lungcan.2019.05.011
  13. FoundationOne CDx. FoundationMedicine.com. Accessed January 9, 2023 https://www.foundationmedicine.com/test/foundationone-cdx
  14. Foundation Medicine received FDA approval for FoundationOne CDx as the companion diagnostic for Tabrecta (capmatinib), the only FDA-approved MET inhibitor for patient with metastatic non-small cell lung cancer with METex14. Press release. Foundation Medicine. May 6, 2020. Accessed January 9, 2023. https://www.foundationmedicine.com/press-releases/0f19426e-6c6b-4d75-8801-789b6f603eb2
  15. Paik PK, Felip E, Veillon R, et al. Tepotinib in non-small-cell lung cancer with MET exon 14 skipping mutations. N Engl J Med. 2020;383(10):931-943. doi:10.1056/NEJMoa2004407
  16. Smit EF, Dooms C, Raskin J, et al. INSIGHT 2: a phase II study of tepotinib plus osimertinib in MET-amplified NSCLC and first-line osimertinib resistance. Future Oncol. 2022;18(9):1039-1054. doi:10.2217/fon-2021-1406
  17. Mazieres J, Kim TM, Lim BK, et al. LBA52 – Tepotinib + osimertinib for EGFRm NSCLC with MET amplification (METamp) after progression on first-line (1L) osimertinib: initial result from the INSIGHT 2 study. Paper presented at: 2022 European Society for Medical Oncology Congress; September 9-13, 2022; Paris, France. Abstract LBA52. OncologyPRO. Accessed January 9, 2023. https://oncologypro.esmo.org/meeting-resources/esmo-congress/tepotinib-osimertinib-for-egfrm-nsclc-with-met-amplification-metamp-after-progression-on-first-line-1l-osimertinib-initial-results-from-the
  18. Wolf J, Seto T, Han JY, et al; GEOMETRY mono-1 Investigators. Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer. N Engl J Med. 2020;383(10):944-957. doi:10.1056/NEJMoa2002787
  19. Lu S, Fang J, Li X, et al. Long-term efficacy, safety, and subgroup analysis of savolitinib in Chinese patients with NSCLCs harboring MET exon 14 skipping alterations. JTO Clin Res Rep. 2022;3(10):100407. doi:10.1016/j.jtocrr.2022.100407
  20. Ahn MJ, De Marinis F, Bonanno L, et al. EP08.02-140 MET biomarker-based preliminary efficacy analysis in SAVANNAH: savolitinib+osimertinib in EGFRm NSCLC post-osimertinib. J Thor Oncol. 2022;17(supp 9):S469-S470. doi:10.1016/j.jtho.2022.07.823
  21. Lu S, Xu W, Telaranta-Keerie A, Jia N, Hartmaier R. EP08.02-138 SAFFRON: Ph3 savolitinib + osimertinib vs chemotherapy in EGFRm NSCLC with MET overexpression/amplification post-osimertinib. J Thor Oncol. 2022;17(supp 9):S468-S469. doi:10.1016/j.jtho.2022.07.821
  22. FDA grants accelerated approval to tepotinib for metastatic non-small cell lung cancer. Press release. FDA. February 3, 2021. Accessed January 9, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tepotinib-metastatic-non-small-cell-lung-cancer
  23. FDA approves capmatinib for metastatic non-small cell lung cancer. Press release. FDA. August 11, 2022. Accessed January 9, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-capmatinib-metastatic-non-small-cell-lung-cancer
  24. Gan HK, Millward M, Hua Y, et al. First-in-human phase I study of the selective MET inhibitor, savolitinib, in patients with advanced solid tumors: safety, pharmacokinetics, and antitumor activity. Clin Cancer Res. 2019;25(16):4924-4932. doi:10.1158/1078-0432.CCR-18-1189
  25. Gavine PR, Ren Y, Han L, et al. Volitinib, a potent and highly selective c-Met inhibitor, effectively blocks c-Met signaling and growth in c-MET amplified gastric cancer patient-derived tumor xenograft models. Mol Oncol. 2015;9(1):323-333. doi:10.1016/j.molonc.2014.08.015
  26. Schuller AG, Barry ER, Jones RD, et al. The MET inhibitor AZD6094 (savolitinib, HMPL-504) induces regression in papillary renal cell carcinoma patient-derived xenograft models. Clin Cancer Res. 2015;21(12):2811-2819. doi:10.1158/1078-0432.CCR-14-2685
  27. Yu H, Ahn MJ, Kim SW, et al. Abstract CT032: TATTON phase 1b expansion cohort: osimertinib plus savolitinib for patients (pts) with EGFR-mutant, MET-amplified NSCLC after progression on prior first/second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Cancer Res. 2019;79(suppl 13):CT032. doi:10.1158/1538-7445.AM2019-CT032
  28. Orpathys approved in China for patients with lung cancer and MET gene alterations. Press release. AstraZeneca. June 23, 2021.Accessed January 9, 2023. https://www.astrazeneca.com/media-centre/press-releases/2021/orpathys-approved-in-china-for-patients-with-lung-cancer-and-met-gene-alterations.html
Related Content