The Treatment of a New Entity in Advanced Non-small Cell Lung Cancer: MET Exon 14 Skipping Mutation


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Abstract

Background:MET (MET Proto-Oncogene, Receptor Tyrosine Kinase) exon 14 skipping mutation represents one of the most common MET alterations, accounting for approximately 1-3% of all mutations in advanced lung adenocarcinomas. While until 2020 no specific treatment was available for this subset of patients, as of today, three MET Tyrosine Kinase Inhibitors (TKIs) are currently approved in this setting, namely capmatinib, tepotinib and savolitinib.

Objective:This article aims to provide an extensive overview of the current therapeutic standard of care for exon 14 skipped advanced Non-small Cell Lung Cancer (NSCLC) patients, alongside with mentions of the main future challenges and opportunities.

Conclusion:FDA-approved MET-TKIs currently represent the best option for treating exon 14 skipped advanced NSCLC patients, thanks to their excellent efficacy profile, alongside their manageable safety and tolerability. However, we currently lack specific agents to treat patients progressing on capmatinib or tepotinib, due to a limited understanding of the mechanisms underlying both on- and off-target resistance. In this respect, on-target mutations presently constitute the most explored ones from a mechanistic point of view, and type II MET-TKIs are currently under investigation as the most promising agents capable of overcoming the acquired resistance.

About the authors

Danilo Rocco

Department of Pulmonary Oncology, AORN dei Colli Monaldi

Email: info@benthamscience.net

Luigi Gravara

Department of Precision Medicine, Università degli studi della Campania "Luigi Vanvitelli"

Email: info@benthamscience.net

Giovanni Palazzolo

Division of Medical Oncology, ULSS 15 Cittadella

Email: info@benthamscience.net

Cesare Gridelli

Division of Medical Oncology, S.G. Moscati Hospital

Author for correspondence.
Email: info@benthamscience.net

References

  1. Zhang, Y.; Xia, M.; Jin, K.; Wang, S.; Wei, H.; Fan, C.; Wu, Y.; Li, X.; Li, X.; Li, G.; Zeng, Z.; Xiong, W. Function of the c-Met receptor tyrosine kinase in carcinogenesis and associated therapeutic opportunities. Mol. Cancer, 2018, 17(1), 45. doi: 10.1186/s12943-018-0796-y PMID: 29455668
  2. Giordano, S.; Di Renzo, M.F.; Narsimhan, R.P.; Cooper, C.S.; Rosa, C.; Comoglio, P.M. Biosynthesis of the protein encoded by the c-met proto-oncogene. Oncogene, 1989, 4(11), 1383-1388. PMID: 2554238
  3. Sierra, J.R.; Tsao, M.S. c-MET as a potential therapeutic target and biomarker in cancer. Ther. Adv. Med. Oncol., 2011, 3(S1), S21-S35. doi: 10.1177/1758834011422557 PMID: 22128285
  4. Safaie Qamsari, E.; Safaei Ghaderi, S.; Zarei, B.; Dorostkar, R.; Bagheri, S.; Jadidi-Niaragh, F.; Somi, M.H.; Yousefi, M. The c-Met receptor: Implication for targeted therapies in colorectal cancer. Tumour Biol., 2017, 39(5) doi: 10.1177/1010428317699118 PMID: 28459362
  5. Yang, X.; Liao, H.Y.; Zhang, H.H. Roles of MET in human cancer. Clin. Chim. Acta, 2022, 525, 69-83. doi: 10.1016/j.cca.2021.12.017 PMID: 34951962
  6. Matsumoto, K.; Umitsu, M.; De Silva, D.M.; Roy, A.; Bottaro, D.P. Hepatocyte growth factor/MET in cancer progression and biomarker discovery. Cancer Sci., 2017, 108(3), 296-307. doi: 10.1111/cas.13156 PMID: 28064454
  7. Tolbert, W.D.; Daugherty-Holtrop, J.; Gherardi, E.; Vande Woude, G.; Xu, H.E. Structural basis for agonism and antagonism of hepatocyte growth factor. Proc. Natl. Acad. Sci., 2010, 107(30), 13264-13269. doi: 10.1073/pnas.1005183107 PMID: 20624990
  8. Zhang, J.; Babic, A. Regulation of the MET oncogene: Molecular mechanisms. Carcinogenesis., 2016, 37(4), 345-355. doi: 10.1093/carcin/bgw015 PMID: 26905592
  9. Linossi, E.M.; Estevam, G.O.; Oshima, M.; Fraser, J.S.; Collisson, E.A.; Jura, N. State of the structure address on MET receptor activation by HGF. Biochem. Soc. Trans., 2021, 49(2), 645-661. doi: 10.1042/BST20200394 PMID: 33860789
  10. Modi, V.; Dunbrack, R.L.Jr. Defining a new nomenclature for the structures of active and inactive kinases. Proc. Natl. Acad. Sci., 2019, 116(14), 6818-6827. doi: 10.1073/pnas.1814279116 PMID: 30867294
  11. Treiber, D.K.; Shah, N.P. Ins and outs of kinase DFG motifs. Chem. Biol., 2013, 20(6), 745-746. doi: 10.1016/j.chembiol.2013.06.001 PMID: 23790484
  12. Uchikawa, E.; Chen, Z.; Xiao, G.Y.; Zhang, X.; Bai, X. Structural basis of the activation of c-MET receptor. Nat. Commun., 2021, 12(1), 4074. doi: 10.1038/s41467-021-24367-3 PMID: 34210960
  13. Organ, S.L.; Tsao, M.S. An overview of the c-MET signaling pathway. Ther. Adv. Med. Oncol., 2011, 3(S1), S7-S19. doi: 10.1177/1758834011422556 PMID: 22128289
  14. Raj, S.; Kesari, K.K.; Kumar, A.; Rathi, B.; Sharma, A.; Gupta, P.K.; Jha, S.K.; Jha, N.K.; Slama, P.; Roychoudhury, S.; Kumar, D. Molecular mechanism(s) of regulation(s) of c-MET/HGF signaling in head and neck cancer. Mol. Cancer, 2022, 21(1), 31. doi: 10.1186/s12943-022-01503-1 PMID: 35081970
  15. Sachs, M.; Brohmann, H.; Zechner, D.; Müller, T.; Hülsken, J.; Walther, I.; Schaeper, U.; Birchmeier, C.; Birchmeier, W. Essential role of Gab1 for signaling by the c-Met receptor in vivo. J. Cell Biol., 2000, 150(6), 1375-1384. doi: 10.1083/jcb.150.6.1375 PMID: 10995442
  16. Park, T. Crk and CrkL as therapeutic targets for cancer treatment. Cells, 2021, 10(4), 739. doi: 10.3390/cells10040739 PMID: 33801580
  17. Hervieu, A.; Kermorgant, S. The role of PI3K in met driven cancer: A recap. Front. Mol. Biosci., 2018, 5, 86. doi: 10.3389/fmolb.2018.00086 PMID: 30406111
  18. Rivas, S.; Marín, A.; Samtani, S.; González-Feliú, E.; Armisén, R. MET signaling pathways, resistance mechanisms, and opportunities for target therapies. Int. J. Mol. Sci., 2022, 23(22), 13898. doi: 10.3390/ijms232213898 PMID: 36430388
  19. Trusolino, L.; Comoglio, P.M. Scatter-factor and semaphorin receptors: Cell signalling for invasive growth. Nat. Rev. Cancer, 2002, 2(4), 289-300. doi: 10.1038/nrc779 PMID: 12001990
  20. Andermarcher, E.; Surani, M.A.; Gherardi, E. Co-expression of theHGF/SF andc-met genes during early mouse embryogenesis precedes reciprocal expression in adjacent tissues during organogenesis. Dev. Genet., 1996, 18(3), 254-266. doi: 10.1002/(SICI)1520-6408(1996)18:33.0.CO;2-8 PMID: 8631159
  21. Kolatsi-Joannou, M.; Moore, R.; Winyard, P.J.D.; Woolf, A.S. Expression of hepatocyte growth factor/scatter factor and its receptor, MET, suggests roles in human embryonic organogenesis. Pediatr. Res., 1997, 41(5), 657-665. doi: 10.1203/00006450-199705000-00010 PMID: 9128288
  22. Neuss, S.; Becher, E.; Wöltje, M.; Tietze, L.; Jahnen-Dechent, W. Functional expression of HGF and HGF receptor/c-met in adult human mesenchymal stem cells suggests a role in cell mobilization, tissue repair, and wound healing. Stem Cells, 2004, 22(3), 405-414. doi: 10.1634/stemcells.22-3-405 PMID: 15153617
  23. Chmielowiec, J.; Borowiak, M.; Morkel, M.; Stradal, T.; Munz, B.; Werner, S.; Wehland, J.; Birchmeier, C.; Birchmeier, W. c-Met is essential for wound healing in the skin. J. Cell Biol., 2007, 177(1), 151-162. doi: 10.1083/jcb.200701086 PMID: 17403932
  24. Socinski, M.A.; Pennell, N.A.; Davies, K.D. MET Exon 14 skipping mutations in non-small-cell lung cancer: An overview of biology, clinical outcomes, and testing considerations. JCO Precis. Oncol., 2021, 5, 5. PMID: 34036238
  25. Fujino, T.; Suda, K.; Mitsudomi, T. Lung cancer with MET exon 14 skipping mutation: Genetic feature, current treatments, and future challenges. Lung. Cancer., 2021, 12, 35-50. doi: 10.2147/LCTT.S269307 PMID: 34295201
  26. Hu, H.; Mu, Q.; Bao, Z.; Chen, Y.; Liu, Y.; Chen, J.; Wang, K.; Wang, Z.; Nam, Y.; Jiang, B.; Sa, J.K.; Cho, H.J.; Her, N.G.; Zhang, C.; Zhao, Z.; Zhang, Y.; Zeng, F.; Wu, F.; Kang, X.; Liu, Y.; Qian, Z.; Wang, Z.; Huang, R.; Wang, Q.; Zhang, W.; Qiu, X.; Li, W.; Nam, D.H.; Fan, X.; Wang, J.; Jiang, T. Mutational landscape of secondary glioblastoma guides MET-targeted trial in brain tumor. Cell, 2018, 175(6), 1665-1678.e18. doi: 10.1016/j.cell.2018.09.038 PMID: 30343896
  27. Raghav, K.; Morris, V.; Tang, C.; Morelli, P.; Amin, H.M.; Chen, K.; Manyam, G.C.; Broom, B.; Overman, M.J.; Shaw, K.; Meric-Bernstam, F.; Maru, D.; Menter, D.; Ellis, L.M.; Eng, C.; Hong, D.; Kopetz, S. MET amplification in metastatic colorectal cancer: An acquired response to EGFR inhibition, not a de novo phenomenon. Oncotarget, 2016, 7(34), 54627-54631. doi: 10.18632/oncotarget.10559 PMID: 27421137
  28. 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(9), 569-587. doi: 10.1038/s41571-020-0377-z PMID: 32514147
  29. Maroun, C.R.; Rowlands, T. The Met receptor tyrosine kinase: A key player in oncogenesis and drug resistance. Pharmacol. Ther., 2014, 142(3), 316-338. doi: 10.1016/j.pharmthera.2013.12.014 PMID: 24384534
  30. Graveel, C.R.; Tolbert, D.; Vande Woude, G.F. MET: A critical player in tumorigenesis and therapeutic target. Cold Spring Harb. Perspect. Biol., 2013, 5(7), a009209. doi: 10.1101/cshperspect.a009209 PMID: 23818496
  31. Christensen, J.G.; Burrows, J.; Salgia, R. c-Met as a target for human cancer and characterization of inhibitors for therapeutic intervention. Cancer Lett., 2005, 225(1), 1-26. doi: 10.1016/j.canlet.2004.09.044 PMID: 15922853
  32. Gelsomino, F.; Facchinetti, F.; Haspinger, E.R.; Garassino, M.C.; Trusolino, L.; De Braud, F.; Tiseo, M. Targeting the MET gene for the treatment of non-small-cell lung cancer. Crit. Rev. Oncol. Hematol., 2014, 89(2), 284-299. doi: 10.1016/j.critrevonc.2013.11.006 PMID: 24355409
  33. Awad, M.M.; Oxnard, G.R.; Jackman, D.M.; Savukoski, D.O.; Hall, D.; Shivdasani, P.; Heng, J.C.; Dahlberg, S.E.; Jänne, P.A.; Verma, S.; Christensen, J.; Hammerman, P.S.; Sholl, L.M. MET Exon 14 mutations in non–small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-met overexpression. J. Clin. Oncol., 2016, 34(7), 721-730. doi: 10.1200/JCO.2015.63.4600 PMID: 26729443
  34. Ma, P.C.; Jagadeeswaran, R.; Jagadeesh, S.; Tretiakova, M.S.; Nallasura, V.; Fox, E.A.; Hansen, M.; Schaefer, E.; Naoki, K.; Lader, A.; Richards, W.; Sugarbaker, D.; Husain, A.N.; Christensen, J.G.; Salgia, R. Functional expression and mutations of c-Met and its therapeutic inhibition with SU11274 and small interfering RNA in non-small cell lung cancer. Cancer Res., 2005, 65(4), 1479-1488. doi: 10.1158/0008-5472.CAN-04-2650 PMID: 15735036
  35. Cortot, A.B.; Kherrouche, Z.; Descarpentries, C.; Wislez, M.; Baldacci, S.; Furlan, A.; Tulasne, D. Exon 14 deleted MET receptor as a new biomarker and target in cancers. J. Natl. Cancer Inst., 2017, 109(5) doi: 10.1093/jnci/djw262 PMID: 28376232
  36. Peschard, P.; Ishiyama, N.; Lin, T.; Lipkowitz, S.; Park, M. A conserved DpYR motif in the juxtamembrane domain of the Met receptor family forms an atypical c-Cbl/Cbl-b tyrosine kinase binding domain binding site required for suppression of oncogenic activation. J. Biol. Chem., 2004, 279(28), 29565-29571. doi: 10.1074/jbc.M403954200 PMID: 15123609
  37. Lu, X.; Peled, N.; Greer, J.; Wu, W.; Choi, P.; Berger, A.H.; Wong, S.; Jen, K.Y.; Seo, Y.; Hann, B.; Brooks, A.; Meyerson, M.; Collisson, E.A. MET exon 14 mutation encodes an actionable therapeutic target in lung adenocarcinoma. Cancer Res., 2017, 77(16), 4498-4505. doi: 10.1158/0008-5472.CAN-16-1944 PMID: 28522754
  38. Hashigasako, A.; Machide, M.; Nakamura, T.; Matsumoto, K.; Nakamura, T. Bi-directional regulation of Ser-985 phosphorylation of c-met via protein kinase C and protein phosphatase 2A involves c-Met activation and cellular responsiveness to hepatocyte growth factor. J. Biol. Chem., 2004, 279(25), 26445-26452. doi: 10.1074/jbc.M314254200 PMID: 15075332
  39. Gandino, L.; Longati, P.; Medico, E.; Prat, M.; Comoglio, P.M. Phosphorylation of serine 985 negatively regulates the hepatocyte growth factor receptor kinase. J. Biol. Chem., 1994, 269(3), 1815-1820. doi: 10.1016/S0021-9258(17)42099-0 PMID: 8294430
  40. Awad, M.M.; Lee, J.K.; Madison, R.; Classon, A.; Kmak, J.; Frampton, G.M.; Alexander, B.M.; Venstrom, J.; Schrock, A.B. Characterization of 1,387 NSCLCs with MET exon 14 (METex14) skipping alterations (SA) and potential acquired resistance (AR) mechanisms. J. Clin. Oncol., 2020, 38(15_suppl), 9511. doi: 10.1200/JCO.2020.38.15_suppl.9511
  41. Cheng, T.; Gu, Z.; Song, D.; Liu, S.; Tong, X.; Wu, X.; Lin, Z.; Hong, W. Genomic and clinical characteristics of MET exon14 alterations in a large cohort of Chinese cancer patients revealed distinct features and a novel resistance mechanism for crizotinib. J. Cancer, 2021, 12(3), 644-651. doi: 10.7150/jca.49391 PMID: 33403024
  42. Gow, C.H.; Hsieh, M.S.; Wu, S.G.; Shih, J.Y. A comprehensive analysis of clinical outcomes in lung cancer patients harboring a MET exon 14 skipping mutation compared to other driver mutations in an East Asian population. Lung Cancer, 2017, 103, 82-89. doi: 10.1016/j.lungcan.2016.12.001 PMID: 28024701
  43. Lu, D.; Nagelberg, A.; Chow, J.L.M.; Chen, Y.T.; Michalchuk, Q.; Somwar, R.; Lockwood, W.W. MET exon 14 splice-site mutations preferentially activate KRAS signaling to drive tumourigenesis. Cancer., 2022, 14(6), 1378. doi: 10.3390/cancers14061378 PMID: 35326531
  44. Kim, S.Y.; Yin, J.; Bohlman, S.; Walker, P.; Dacic, S.; Kim, C.; Khan, H.; Liu, S.V.; Ma, P.C.; Nagasaka, M.; Reckamp, K.L.; Abraham, J.; Uprety, D.; Wang, F.; Xiu, J.; Zhang, J.; Cheng, H.; Halmos, B. Characterization of MET exon 14 skipping alterations (in NSCLC) and identification of potential therapeutic targets using whole transcriptome sequencing. JTO. Clin. Res. Rep., 2022, 3(9), 100381. doi: 10.1016/j.jtocrr.2022.100381 PMID: 36082279
  45. Liu, L.; Kalyani, F.S.; Yang, H.; Zhou, C.; Xiong, Y.; Zhu, S.; Yang, N.; Qu, J. Prognosis and concurrent genomic alterations in patients with advanced NSCLC harboring MET amplification or MET exon 14 skipping mutation treated with MET inhibitor: A retrospective study. Front. Oncol., 2021, 11, 649766. doi: 10.3389/fonc.2021.649766 PMID: 34249687
  46. Lee, J.K.; Madison, R.; Classon, A.; Gjoerup, O.; Rosenzweig, M.; Frampton, G.M.; Alexander, B.M.; Oxnard, G.R.; Venstrom, J.M.; Awad, M.M.; Schrock, A.B. Characterization of non–small-cell lung cancers with MET exon 14 skipping alterations detected in tissue or liquid: Clinicogenomics and real-world treatment patterns. JCO Precis. Oncol., 2021, 5(5), 1354-1376. doi: 10.1200/PO.21.00122 PMID: 34476332
  47. Jamme, P.; Fernandes, M.; Copin, M.C.; Descarpentries, C.; Escande, F.; Morabito, A.; Grégoire, V.; Jamme, M.; Baldacci, S.; Tulasne, D.; Kherrouche, Z.; Cortot, A.B. Alterations in the PI3K pathway drive resistance to MET inhibitors in NSCLC harboring MET exon 14 skipping mutations. J. Thorac. Oncol., 2020, 15(5), 741-751. doi: 10.1016/j.jtho.2020.01.027 PMID: 32169477
  48. Schrock, A.B.; Frampton, G.M.; Suh, J.; Chalmers, Z.R.; Rosenzweig, M.; Erlich, R.L.; Halmos, B.; Goldman, J.; Forde, P.; Leuenberger, K.; Peled, N.; Kalemkerian, G.P.; Ross, J.S.; Stephens, P.J.; Miller, V.A.; Ali, S.M.; Ou, S.H.I. Characterization of 298 patients with lung cancer harboring MET exon 14 skipping alterations. J. Thorac. Oncol., 2016, 11(9), 1493-1502. doi: 10.1016/j.jtho.2016.06.004 PMID: 27343443
  49. 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(10), 2085-2091. doi: 10.1093/annonc/mdy334 PMID: 30165371
  50. Hur, J.Y.; Ku, B.M.; Shim, J.H.; Jung, H.A.; Sun, J.M.; Lee, S.H.; Ahn, J.S.; Park, K.; Ahn, M.J. Characteristics and clinical outcomes of non-small cell lung cancer patients in Korea with MET exon 14 skipping. In Vivo, 2020, 34(3), 1399-1406. doi: 10.21873/invivo.11920 PMID: 32354937
  51. Huang, C.; Zou, Q.; Liu, H.; Qiu, B.; Li, Q.; Lin, Y.; Liang, Y. Management of non-small cell lung cancer patients with MET exon 14 skipping mutations. Curr. Treat. Options Oncol., 2020, 21(4), 33. doi: 10.1007/s11864-020-0723-5 PMID: 32306194
  52. Bittoni, M.; Yang, J.C.H.; Shih, J.Y.; Peled, N.; Smit, E.F.; Camidge, D.R.; Arasada, R.R.; Oksen, D.; Boutmy, E.; Stroh, C.; Johne, A.; Carbone, D.P.; Paik, P.K. Real-world insights into patients with advanced NSCLC and MET alterations. Lung Cancer, 2021, 159, 96-106. doi: 10.1016/j.lungcan.2021.06.015 PMID: 34320421
  53. Wong, S.K.; Alex, D.; Bosdet, I.; Hughesman, C.; Karsan, A.; Yip, S.; Ho, C. MET exon 14 skipping mutation positive non-small cell lung cancer: Response to systemic therapy. Lung Cancer, 2021, 154, 142-145. doi: 10.1016/j.lungcan.2021.02.030 PMID: 33667719
  54. Brazel, D.; Zhang, S.; Nagasaka, M. Spotlight on tepotinib and capmatinib for non-small cell lung cancer with MET exon 14 skipping mutation. Lung. Cancer., 2022, 13, 33-45. doi: 10.2147/LCTT.S360574 PMID: 35592355
  55. Wise-Draper, T.M.; Gulati, S.; Palackdharry, S.; Hinrichs, B.H.; Worden, F.P.; Old, M.O.; Dunlap, N.E.; Kaczmar, J.M.; Patil, Y.; Riaz, M.K.; Tang, A.; Mark, J.; Zender, C.; Gillenwater, A.M.; Bell, D.; Kurtzweil, N.; Mathews, M.; Allen, C.L.; Mierzwa, M.L.; Casper, K.; Jandarov, R.; Medvedovic, M.; Lee, J.J.; Harun, N.; Takiar, V.; Gillison, M. Phase II clinical trial of neoadjuvant and adjuvant pembrolizumab in resectable local–regionally advanced head and neck squamous cell carcinoma. Clin. Cancer Res., 2022, 28(7), 1345-1352. doi: 10.1158/1078-0432.CCR-21-3351 PMID: 35338369
  56. Mathieu, L.N.; Larkins, E.; Akinboro, O.; Roy, P.; Amatya, A.K.; Fiero, M.H.; Mishra-Kalyani, P.S.; Helms, W.S.; Myers, C.E.; Skinner, A.M.; Aungst, S.; Jin, R.; Zhao, H.; Xia, H.; Zirkelbach, J.F.; Bi, Y.; Li, Y.; Liu, J.; Grimstein, M.; Zhang, X.; Woods, S.; Reece, K.; Abukhdeir, A.M.; Ghosh, S.; Philip, R.; Tang, S.; Goldberg, K.B.; Pazdur, R.; Beaver, J.A.; Singh, H. FDA approval summary: Capmatinib and tepotinib for the treatment of metastatic NSCLC harboring MET exon 14 skipping mutations or alterations. Clin. Cancer Res., 2022, 28(2), 249-254. doi: 10.1158/1078-0432.CCR-21-1566 PMID: 34344795
  57. Dhillon, S. Capmatinib: First approval. Drugs, 2020, 80(11), 1125-1131. doi: 10.1007/s40265-020-01347-3 PMID: 32557339
  58. Markham, A. Tepotinib: First approval. Drugs, 2020, 80(8), 829-833. doi: 10.1007/s40265-020-01317-9 PMID: 32361823
  59. Jia, H.; Dai, G.; Weng, J.; Zhang, Z.; Wang, Q.; Zhou, F.; Jiao, L.; Cui, Y.; Ren, Y.; Fan, S.; Zhou, J.; Qing, W.; Gu, Y.; Wang, J.; Sai, Y.; Su, W. Discovery of (S)-1-(1-(Imidazo1,2-apyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-1,2,3triazolo4,5-bpyrazine (volitinib) as a highly potent and selective mesenchymal-epithelial transition factor (c-Met) inhibitor in clinical development for treatment of cancer. J. Med. Chem., 2014, 57(18), 7577-7589. doi: 10.1021/jm500510f PMID: 25148209
  60. Zhu, X.; Lu, Y.; Lu, S. Landscape of savolitinib development for the treatment of non-small cell lung cancer with MET alteration—a narrative review. Cancers., 2022, 14(24), 6122. doi: 10.3390/cancers14246122 PMID: 36551608
  61. Wolf, J.; Seto, T.; Han, J.Y.; Reguart, N.; Garon, E.B.; Groen, H.J.M.; Tan, D.S.W.; Hida, T.; de Jonge, M.; Orlov, S.V.; Smit, E.F.; Souquet, P.J.; Vansteenkiste, J.; Hochmair, M.; Felip, E.; Nishio, M.; Thomas, M.; Ohashi, K.; Toyozawa, R.; Overbeck, T.R.; de Marinis, F.; Kim, T.M.; Laack, E.; Robeva, A.; Le Mouhaer, S.; Waldron-Lynch, M.; Sankaran, B.; Balbin, O.A.; Cui, X.; Giovannini, M.; Akimov, M.; Heist, R.S. 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 PMID: 32877583
  62. Wolf, J; Garon, EB; Groen, HJM; Tan, DS-W; Robeva, A; Mouhaer, SL Capmatinib in MET exon 14-mutated, advanced NSCLC: Updated results from the GEOMETRY mono-1 study. N Engl J Med., 2021, 39(S15), 9020.
  63. Paik, P.K.; Felip, E.; Veillon, R.; Sakai, H.; Cortot, A.B.; Garassino, M.C.; Mazieres, J.; Viteri, S.; Senellart, H.; Van Meerbeeck, J.; Raskin, J.; Reinmuth, N.; Conte, P.; Kowalski, D.; Cho, B.C.; Patel, J.D.; Horn, L.; Griesinger, F.; Han, J.Y.; Kim, Y.C.; Chang, G.C.; Tsai, C.L.; Yang, J.C.H.; Chen, Y.M.; Smit, E.F.; van der Wekken, A.J.; Kato, T.; Juraeva, D.; Stroh, C.; Bruns, R.; Straub, J.; Johne, A.; Scheele, J.; Heymach, J.V.; Le, X. 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 PMID: 32469185
  64. Veillon, R; Sakai, H; Le, X; Felip, E; Garassino, MC; Cortot, A Tepotinib safety in MET Exon 14 (METex14) skipping NSCLC: Updated results from the VISION trial. J Thorac Oncol, 2021, 16(3), S231.
  65. Le, X.; Sakai, H.; Felip, E.; Veillon, R.; Garassino, M.C.; Raskin, J.; Cortot, A.B.; Viteri, S.; Mazieres, J.; Smit, E.F.; Thomas, M.; Iams, W.T.; Cho, B.C.; Kim, H.R.; Yang, J.C.H.; Chen, Y.M.; Patel, J.D.; Bestvina, C.M.; Park, K.; Griesinger, F.; Johnson, M.; Gottfried, M.; Britschgi, C.; Heymach, J.; Sikoglu, E.; Berghoff, K.; Schumacher, K.M.; Bruns, R.; Otto, G.; Paik, P.K. Tepotinib efficacy and safety in patients with MET exon 14 skipping NSCLC: outcomes in patient subgroups from the VISION study with relevance for clinical practice. Clin. Cancer Res., 2022, 28(6), 1117-1126. doi: 10.1158/1078-0432.CCR-21-2733 PMID: 34789481
  66. Lu, S.; Fang, J.; Li, X.; Cao, L.; Zhou, J.; Guo, Q.; Liang, Z.; Cheng, Y.; Jiang, L.; Yang, N.; Han, Z.; Shi, J.; Chen, Y.; Xu, H.; Zhang, H.; Chen, G.; Ma, R.; Sun, S.; Fan, Y.; Li, J.; Luo, X.; Wang, L.; Ren, Y.; Su, W. Once-daily savolitinib in Chinese patients with pulmonary sarcomatoid carcinomas and other non-small-cell lung cancers harbouring MET exon 14 skipping alterations: a multicentre, single-arm, open-label, phase 2 study. Lancet Respir. Med., 2021, 9(10), 1154-1164. doi: 10.1016/S2213-2600(21)00084-9 PMID: 34166627
  67. Prabhash, K.; Noronha, V.; Joshi, A.; Desai, S.; Sahu, A. Crizotinib: A comprehensive review. South Asian J. Cancer, 2013, 2(2), 91-97. doi: 10.4103/2278-330X.110506 PMID: 24455567
  68. Drilon, A.E.; Camidge, D.R.; Ou, S.H.I.; Clark, J.W.; Socinski, M.A.; Weiss, J.; Riely, G.J.; Winter, M.; Wang, S.C.; Monti, K.; Wilner, K.D.; Paik, P.K. Efficacy and safety of crizotinib in patients (pts) with advanced MET exon 14-altered non-small cell lung cancer (NSCLC). J. Clin. Oncol., 2016, 34(S15), 108. doi: 10.1200/JCO.2016.34.15_suppl.108
  69. Drilon, A.; Clark, J.W.; Weiss, J.; Ou, S.H.I.; Camidge, D.R.; Solomon, B.J.; Otterson, G.A.; Villaruz, L.C.; Riely, G.J.; Heist, R.S.; Awad, M.M.; Shapiro, G.I.; Satouchi, M.; Hida, T.; Hayashi, H.; Murphy, D.A.; Wang, S.C.; Li, S.; Usari, T.; Wilner, K.D.; Paik, P.K. Antitumor activity of crizotinib in lung cancers harboring a MET exon 14 alteration. Nat. Med., 2020, 26(1), 47-51. doi: 10.1038/s41591-019-0716-8 PMID: 31932802
  70. Landi, L.; Chiari, R.; Tiseo, M.; D’Incà, F.; Dazzi, C.; Chella, A.; Delmonte, A.; Bonanno, L.; Giannarelli, D.; Cortinovis, D.L.; de Marinis, F.; Borra, G.; Morabito, A.; Gridelli, C.; Galetta, D.; Barbieri, F.; Grossi, F.; Capelletto, E.; Minuti, G.; Mazzoni, F.; Verusio, C.; Bria, E.; Alì, G.; Bruno, R.; Proietti, A.; Fontanini, G.; Crinò, L.; Cappuzzo, F. Crizotinib in MET -Deregulated or ROS1 -rearranged pretreated non–small cell lung cancer (METROS): A phase II, prospective, multicenter, two-arms trial. Clin. Cancer Res., 2019, 25(24), 7312-7319. doi: 10.1158/1078-0432.CCR-19-0994 PMID: 31416808
  71. Moro-Sibilot, D.; Cozic, N.; Pérol, M.; Mazières, J.; Otto, J.; Souquet, P.J.; Bahleda, R.; Wislez, M.; Zalcman, G.; Guibert, S.D.; Barlési, F.; Mennecier, B.; Monnet, I.; Sabatier, R.; Bota, S.; Dubos, C.; Verriele, V.; Haddad, V.; Ferretti, G.; Cortot, A.; De Fraipont, F.; Jimenez, M.; Hoog-Labouret, N.; Vassal, G. Crizotinib in c-MET- or ROS1-positive NSCLC: Results of the AcSé phase II trial. Ann. Oncol., 2019, 30(12), 1985-1991. doi: 10.1093/annonc/mdz407 PMID: 31584608
  72. Middleton, G.; Fletcher, P.; Popat, S.; Savage, J.; Summers, Y.; Greystoke, A.; Gilligan, D.; Cave, J.; O’Rourke, N.; Brewster, A.; Toy, E.; Spicer, J.; Jain, P.; Dangoor, A.; Mackean, M.; Forster, M.; Farley, A.; Wherton, D.; Mehmi, M.; Sharpe, R.; Mills, T.C.; Cerone, M.A.; Yap, T.A.; Watkins, T.B.K.; Lim, E.; Swanton, C.; Billingham, L. The national lung matrix trial of personalized therapy in lung cancer. Nature, 2020, 583(7818), 807-812. doi: 10.1038/s41586-020-2481-8 PMID: 32669708
  73. Study of crizotinib for ROS1 and MET activated lung cancer. NCT04084717, 2019.
  74. Targeted therapy directed by genetic testing in treating patients with advanced refractory solid tumors, lymphomas, or multiple myeloma. NCT02465060, 2023.
  75. APL-101 study of subjects with NSCLC with c-Met EXON 14 skip mutations and c-Met dysregulation advanced solid tumors (SPARTA). NCT03175224, 2022.
  76. Study of TPX-0022 in patients with advanced NSCLC, gastric cancer or solid tumors harboring genetic alterations in MET (SHIELD-1). NCT03993873, 2023.
  77. Cabozantinib in patients with RET fusion-positive advanced non-small cell lung cancer and those with other genotypes: ROS1 or NTRK fusions or increased MET or AXL activity. NCT01639508, 2023.
  78. Merestinib In non-small cell lung cancer and solid tumors. NCT02920996, 2023.
  79. Assessment of anti-tumor and safety in glumetinib in patients with c-MET-positive non-small cell lung cancer. NCT04270591, 2022.
  80. Singh, N.; Temin, S.; Baker, S., Jr; Blanchard, E.; Brahmer, J.R.; Celano, P.; Duma, N.; Ellis, P.M.; Elkins, I.B.; Haddad, R.Y.; Hesketh, P.J.; Jain, D.; Johnson, D.H.; Leighl, N.B.; Mamdani, H.; Masters, G.; Moffitt, P.R.; Phillips, T.; Riely, G.J.; Robinson, A.G.; Rosell, R.; Schiller, J.H.; Schneider, B.J.; Spigel, D.R.; Jaiyesimi, I.A. Therapy for stage IV non–small-cell lung cancer with driver alterations: ASCO living guideline. J. Clin. Oncol., 2022, 40(28), 3310-3322. doi: 10.1200/JCO.22.00824 PMID: 35816666
  81. Hanna, N.H.; Robinson, A.G.; Temin, S.; Baker, S., Jr; Brahmer, J.R.; Ellis, P.M.; Gaspar, L.E.; Haddad, R.Y.; Hesketh, P.J.; Jain, D.; Jaiyesimi, I.; Johnson, D.H.; Leighl, N.B.; Moffitt, P.R.; Phillips, T.; Riely, G.J.; Rosell, R.; Schiller, J.H.; Schneider, B.J.; Singh, N.; Spigel, D.R.; Tashbar, J.; Masters, G. Therapy for stage IV non–small-cell lung cancer with driver alterations: ASCO and OH (CCO) joint guideline update. J. Clin. Oncol., 2021, 39(9), 1040-1091. doi: 10.1200/JCO.20.03570 PMID: 33591844
  82. Rocco, D.; Battiloro, C.; Gravara, L.D.; Gridelli, C. Advanced non-small cell lung cancer with activating epidermal growth factor receptor mutation: First line treatment and beyond. Rev. Recent Clin. Trials, 2019, 14(2), 120-128. doi: 10.2174/1574887114666181205155211 PMID: 30520383
  83. Lin, J.J.; Choudhury, N.J.; Yoda, S.; Zhu, V.W.; Johnson, T.W.; Sakhtemani, R.; Dagogo-Jack, I.; Digumarthy, S.R.; Lee, C.; Do, A.; Peterson, J.; Prutisto-Chang, K.; Malik, W.; Hubbeling, H.G.; Langenbucher, A.; Schoenfeld, A.J.; Falcon, C.J.; Temel, J.S.; Sequist, L.V.; Yeap, B.Y.; Lennerz, J.K.; Shaw, A.T.; Lawrence, M.S.; Ou, S.H.I.; Hata, A.N.; Drilon, A.; Gainor, J.F. Spectrum of mechanisms of resistance to crizotinib and lorlatinib in ROS1 fusion–positive lung cancer. Clin. Cancer Res., 2021, 27(10), 2899-2909. doi: 10.1158/1078-0432.CCR-21-0032 PMID: 33685866
  84. Facchinetti, F.; Lacroix, L.; Mezquita, L.; Scoazec, J.Y.; Loriot, Y.; Tselikas, L.; Gazzah, A.; Rouleau, E.; Adam, J.; Michiels, S.; Massard, C.; André, F.; Olaussen, K.A.; Vassal, G.; Howarth, K.; Besse, B.; Soria, J.C.; Friboulet, L.; Planchard, D. Molecular mechanisms of resistance to BRAF and MEK inhibitors in BRAFV600E non–small cell lung cancer. Eur. J. Cancer, 2020, 132, 211-223. doi: 10.1016/j.ejca.2020.03.025 PMID: 32388065
  85. Rocco, D.; Battiloro, C.; Della Gravara, L.; Gridelli, C. Safety and tolerability of anaplastic lymphoma kinase inhibitors in non-small-cell lung cancer. Drug Saf., 2019, 42(2), 199-209. doi: 10.1007/s40264-018-0771-y PMID: 30649741
  86. Addeo, A.; Banna, G.L.; Friedlaender, A. KRAS G12C mutations in NSCLC: From target to resistance. Cancers., 2021, 13(11), 2541. doi: 10.3390/cancers13112541 PMID: 34064232
  87. Rocco, D.; Sapio, L.; Della Gravara, L.; Naviglio, S.; Gridelli, C. Treatment of advanced non-small cell lung cancer with RET fusions: Reality and hopes. Int. J. Mol. Sci., 2023, 24(3), 2433. doi: 10.3390/ijms24032433 PMID: 36768754
  88. Fujino, T.; Kobayashi, Y.; Suda, K.; Koga, T.; Nishino, M.; Ohara, S.; Chiba, M.; Shimoji, M.; Tomizawa, K.; Takemoto, T.; Mitsudomi, T. Sensitivity and resistance of MET exon 14 mutations in lung cancer to eight MET tyrosine kinase inhibitors in vitro. J. Thorac. Oncol., 2019, 14(10), 1753-1765. doi: 10.1016/j.jtho.2019.06.023 PMID: 31279006
  89. Vijayan, R.S.K.; He, P.; Modi, V.; Duong-Ly, K.C.; Ma, H.; Peterson, J.R.; Dunbrack, R.L., Jr; Levy, R.M. Conformational analysis of the DFG-out kinase motif and biochemical profiling of structurally validated type II inhibitors. J. Med. Chem., 2015, 58(1), 466-479. doi: 10.1021/jm501603h PMID: 25478866
  90. Fujino, T.; Suda, K.; Koga, T.; Hamada, A.; Ohara, S.; Chiba, M.; Shimoji, M.; Takemoto, T.; Soh, J.; Mitsudomi, T. Foretinib can overcome common on-target resistance mutations after capmatinib/tepotinib treatment in NSCLCs with MET exon 14 skipping mutation. J. Hematol. Oncol., 2022, 15(1), 79. doi: 10.1186/s13045-022-01299-z PMID: 35690785
  91. Recondo, G.; Bahcall, M.; Spurr, L.F.; Che, J.; Ricciuti, B.; Leonardi, G.C.; Lo, Y.C.; Li, Y.Y.; Lamberti, G.; Nguyen, T.; Milan, M.S.D.; Venkatraman, D.; Umeton, R.; Paweletz, C.P.; Albayrak, A.; Cherniack, A.D.; Price, K.S.; Fairclough, S.R.; Nishino, M.; Sholl, L.M.; Oxnard, G.R.; Jänne, P.A.; Awad, M.M. Molecular mechanisms of acquired resistance to MET tyrosine kinase inhibitors in patients with MET exon 14–mutant NSCLC. Clin. Cancer Res., 2020, 26(11), 2615-2625. doi: 10.1158/1078-0432.CCR-19-3608 PMID: 32034073
  92. Bahcall, M.; Paweletz, C.P.; Kuang, Y.; Taus, L.J.; Sim, T.; Kim, N.D.; Dholakia, K.H.; Lau, C.J.; Gokhale, P.C.; Chopade, P.R.; Hong, F.; Wei, Z.; Köhler, J.; Kirschmeier, P.T.; Guo, J.; Guo, S.; Wang, S.; Jänne, P.A. Combination of type I and type II MET tyrosine kinase inhibitors as therapeutic approach to prevent resistance. Mol. Cancer Ther., 2022, 21(2), 322-335. doi: 10.1158/1535-7163.MCT-21-0344 PMID: 34789563
  93. Rotow, J.K.; Gui, P.; Wu, W.; Raymond, V.M.; Lanman, R.B.; Kaye, F.J.; Peled, N.; Fece de la Cruz, F.; Nadres, B.; Corcoran, R.B.; Yeh, I.; Bastian, B.C.; Starostik, P.; Newsom, K.; Olivas, V.R.; Wolff, A.M.; Fraser, J.S.; Collisson, E.A.; McCoach, C.E.; Camidge, D.R.; Pacheco, J.; Bazhenova, L.; Li, T.; Bivona, T.G.; Blakely, C.M. Co-occurring alterations in the RAS–MAPK pathway limit response to MET inhibitor treatment in MET exon 14 skipping mutation-positive lung cancer. Clin. Cancer Res., 2020, 26(2), 439-449. doi: 10.1158/1078-0432.CCR-19-1667 PMID: 31548343
  94. Guo, R.; Offin, M.; Brannon, A.R.; Chang, J.; Chow, A.; Delasos, L.; Girshman, J.; Wilkins, O.; McCarthy, C.G.; Makhnin, A.; Falcon, C.; Scott, K.; Tian, Y.; Cecchi, F.; Hembrough, T.; Alex, D.; Shen, R.; Benayed, R.; Li, B.T.; Rudin, C.M.; Kris, M.G.; Arcila, M.E.; Rekhtman, N.; Paik, P.; Zehir, A.; Drilon, A. MET exon 14–altered lung cancers and MET inhibitor resistance. Clin. Cancer Res., 2021, 27(3), 799-806. doi: 10.1158/1078-0432.CCR-20-2861 PMID: 33172896
  95. Drusbosky, L.M.; Dawar, R.; Rodriguez, E.; Ikpeazu, C.V. Therapeutic strategies in METex14 skipping mutated non-small cell lung cancer. J. Hematol. Oncol., 2021, 14(1), 129. doi: 10.1186/s13045-021-01138-7 PMID: 34425853
  96. Suzawa, K.; Offin, M.; Lu, D.; Kurzatkowski, C.; Vojnic, M.; Smith, R.S.; Sabari, J.K.; Tai, H.; Mattar, M.; Khodos, I.; de Stanchina, E.; Rudin, C.M.; Kris, M.G.; Arcila, M.E.; Lockwood, W.W.; Drilon, A.; Ladanyi, M.; Somwar, R. Activation of KRAS mediates resistance to targeted therapy in MET exon 14–mutant non–small cell lung cancer. Clin. Cancer Res., 2019, 25(4), 1248-1260. doi: 10.1158/1078-0432.CCR-18-1640 PMID: 30352902
  97. Mok, T.S.; Wu, Y.L.; Ahn, M.J.; Garassino, M.C.; Kim, H.R.; Ramalingam, S.S.; Shepherd, F.A.; He, Y.; Akamatsu, H.; Theelen, W.S.M.E.; Lee, C.K.; Sebastian, M.; Templeton, A.; Mann, H.; Marotti, M.; Ghiorghiu, S.; Papadimitrakopoulou, V.A. Osimertinib or platinum–pemetrexed in EGFR T790M–positive lung cancer. N. Engl. J. Med., 2017, 376(7), 629-640. doi: 10.1056/NEJMoa1612674 PMID: 27959700
  98. Leonetti, A.; Sharma, S.; Minari, R.; Perego, P.; Giovannetti, E.; Tiseo, M. Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer. Br. J. Cancer, 2019, 121(9), 725-737. doi: 10.1038/s41416-019-0573-8 PMID: 31564718
  99. Pan, Y.; Deng, C.; Qiu, Z.; Cao, C.; Wu, F. The resistance mechanisms and treatment strategies for ALK-rearranged non-small cell lung cancer. Front. Oncol., 2021, 11, 713530. doi: 10.3389/fonc.2021.713530 PMID: 34660278
  100. Solomon, B.J.; Besse, B.; Bauer, T.M.; Felip, E.; Soo, R.A.; Camidge, D.R.; Chiari, R.; Bearz, A.; Lin, C.C.; Gadgeel, S.M.; Riely, G.J.; Tan, E.H.; Seto, T.; James, L.P.; Clancy, J.S.; Abbattista, A.; Martini, J.F.; Chen, J.; Peltz, G.; Thurm, H.; Ou, S.H.I.; Shaw, A.T. Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study. Lancet Oncol., 2018, 19(12), 1654-1667. doi: 10.1016/S1470-2045(18)30649-1 PMID: 30413378
  101. Lin, J.J.; Shaw, A.T. Refining precision cancer therapy in ALK-positive NSCLC. EBioMedicine, 2019, 41, 9-10. doi: 10.1016/j.ebiom.2019.01.059 PMID: 30737082
  102. Planchard, D.; Popat, S.; Kerr, K.; Novello, S.; Smit, E.F.; Faivre-Finn, C.; Mok, T.S.; Reck, M.; Van Schil, P.E.; Hellmann, M.D. Metastatic non-small cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol., 2018, 29(S4), iv192-iv237. doi: 10.1093/annonc/mdy275
  103. Nieva, J.; Reckamp, K.L.; Potter, D.; Taylor, A.; Sun, P. Retrospective analysis of real-world management of EGFR-mutated advanced NSCLC, after first-line EGFR-TKI treatment: US treatment patterns, attrition, and survival data. Drugs Real World Outcomes, 2022, 9(3), 333-345. doi: 10.1007/s40801-022-00302-w PMID: 35661118
  104. Cortellini, A.; Ficorella, C.; Crisci, R.; Divisi, D. A reflection on the actual place of osimertinib in the treatment algorithm of EGFR-positive non-small cell lung cancer patients. J. Thorac. Dis., 2020, 12(10), 6107-6111. doi: 10.21037/jtd-20-1733 PMID: 33209443
  105. Lee, C.S.; Milone, M.; Seetharamu, N. Osimertinib in EGFR-mutated lung cancer: A review of the existing and emerging clinical data. OncoTargets Ther., 2021, 14, 4579-4597. doi: 10.2147/OTT.S227032 PMID: 34471361
  106. Lazzari, C.; Gregorc, V.; Karachaliou, N.; Rosell, R.; Santarpia, M. Mechanisms of resistance to osimertinib. J. Thorac. Dis., 2020, 12(5), 2851-2858. doi: 10.21037/jtd.2019.08.30 PMID: 32642198
  107. Yu, H.; Goldberg, S.; Le, X. ORCHARD: A phase II platform study in patients with advanced NSCLC who have progressed on first-line osimertinib therapy. J Thorac Oncol., 2019, 14(10), S647. doi: 10.1016/j.jtho.2019.08.1366
  108. Phase 2 Platform Study in Patients with Advanced Non-Small Lung Cancer who Progressed on First-Line Osimertinib Therapy (ORCHARD) (ORCHARD); clinicaltrials.org internet. ClinicalTrials.gov Identifier: NCT03944772 Available from: https://www.clinicaltrials.gov/ct2/show/NCT03944772. Accessed May 2023

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