New approaches in RET and MET in NSCLC
DOI:
https://doi.org/10.32932/gecp.2022.10.034Abstract
The era of precision medicine has resulted in the identification of several genomic alterations that can be targeted with novel therapies. In lung adenocarcinomas, a histology that accounts for nearly 50% of all cases of lung cancer, a few genomic targets have been linked with effective targeted therapies. For patients with advanced-stage lung adenocarcinomas, molecular testing is now a standard part of diagnostic workup; for patients that have specific driver molecular events, targeted therapies have resulted in substantial improvement in efficacy without excessive toxicity.Downloads
References
Takahashi M, Ritz J, Cooper GM. Activation of a novel human transforming gene, ret, by DNA rearrangement. Cell. 1985;42:581-8.
Takahashi M. The GDNF/RET signaling pathway and human diseases. Cytokine Growth Factor Rev. 2001;12:361-73.
Raue F, Frank -Raue K. Thyroid cancer: risk-stratified management and individualized therapy. Clin Cancer Res. 2016;22:5012-21.
Lipson D, Capelletti M, Yelensky R, et al. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med. 2012;18:382-4.
Gautschi O, Milia J, Filleron T, et al. Targeting RET in patients with RET -rearranged lung cancers: results from the global, multicenter RET registry. J Clin Oncol. 2017;35:1403-10.
Bronte G, Ulivi P, Verlicchi A, Cravero P, Delmonte A, Crinò L. Targeting RET -rearranged non -small-cell lung cancer: future prospects. Lung Cancer (Auckl). 2019;10:27-36.
Lindeman NI, Cagle PT, Aisner DL, et al. Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: guideline from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. J Thorac Oncol. 2018;13:323-8.
Drilon A, Rekhtman N, Arcila M, et al. Cabozantinib in patients with advanced RET -rearranged non -small-cell lung cancer: an open -label, single -centre, phase 2, single -arm trial. Lancet Oncol. 2016;17:1653-60.
Yoh K, Seto T, Satouchi M, et al. Vandetanib in patients with previously treated RET -rearranged advanced non -small -cell lung cancer (LURET): na open -label, multicentre phase 2 trial. Lancet Respir Med. 2017;5:42-50.
Hida T, Velcheti V, Reckamp KL, et al. A phase 2 study of lenvatinib in patients with RET fusion-positive lung adenocarcinoma. Lung Cancer. 2019;138:124-30.
Drilon A, Oxnard GR, Tan DSW, et al. Efficacy of Selpercatinib in RET Fusion -Positive Non -Small-Cell Lung Cancer. N Engl J Med. 2020 Aug 27; 383(9):813 -24. doi: 10.1056/NEJMoa2005653. PMID: 32846060; PMCID: PMC7506467.
Subbiah V, Gainor JF, Oxnard GR, et al. Intracranial Efficacy of Selpercatinib in RET Fusion -Positive Non -Small Cell Lung Cancers on the LIBRETTO -001 Trial. Clin Cancer Res. 2021 Aug 1;27(15):4160 -7. doi: 10.1158/1078 -0432.CCR -21 -0800. Epub 2021 Jun 4. PMID: 34088726; PMCID: PMC8447251.
Gainor JF, Curigliano G, Kim DW, et al. Pralsetinib for RET fusion -positive non -small -cell lung cancer (ARROW): a multi -cohort, open -label, phase 1/2 study. Lancet Oncol. 2021 Jul;22(7):959 -69. doi: 10.1016/S1470 -2045(21)00247 -3. Epub 2021 Jun 9. Erratum in: Lancet Oncol. 2021 Aug;22(8):e347. PMID: 34118197.
Gainor JF, Lee DH, Curigliano G, Doebele RC, et al. Clinical activity and tolerability of BLU -667, a highly potent and selective RET inhibitor, in patients with advanced RET -fusion+ non -small cell lung cancer. J Clin Oncol. 2019;37S:ASCO #9008.
Dong, Y., Xu, J., Sun, B. et al. MET -Targeted Therapies and Clinical Outcomes: A Systematic Literature Review. Mol Diagn Ther 26, 203-27 (2022).
Le X, Hong L, Hensel C, Chen R, Kemp H, Coleman N, Ciunci CA, Liu SV, Negrao MV, Yen J, Xia X, Scheuenpflug J, Stroh C, Juraeva D, Tsao A, Hong D, Raymond V, Paik P, Zhang J, Heymach JV. Land-scape and Clonal Dominance of Co -occurring Genomic Alterations in Non -Small -Cell Lung Cancer Harboring MET Exon 14 Skipping. JCO Precis Oncol. 2021
Zhang YL, Yuan JQ, Wang KF, Fu XH, Han XR, Threapleton D, Yang ZY, Mao C, Tang JL. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta -analysis. Oncotarget. 2016 Nov 29;7(48): 78985 -93. doi: 10.18632/oncotarget.12587. PMID: 27738317; PMCID: PMC5346692.
Drilon, A., Clark, J.W., Weiss, J. et al. Antitumor activity of crizotinib in lung cancers harboring a MET exon 14 alteration. Nat Med 26, 47-51 (2020).
Paik PK, Felip E, Veillon R, Sakai H, Cortot AB, Garassino MC, Mazieres J, Viteri S, Senellart H, Van Meerbeeck J, Raskin J, Reinmuth N, Conte P, Kowalski D, Cho BC, Patel JD, Horn L, Griesinger F, Han JY, Kim YC, Chang GC, Tsai CL, Yang JC, Chen YM, Smit EF, van der Wekken AJ, Kato T, Juraeva D, Stroh C, Bruns R, Straub J, Johne A, Scheele J, Heymach JV, Le X. Tepotinib in Non-Small -Cell Lung Cancer with MET Exon 14 Skipping Mutations. N Engl J Med. 2020 Sep 3; 383(10):931 -43. doi: 10.1056/NEJMoa2004407.
Le X, Sakai H, Felip E, Veillon R, Garassino MC, Raskin J, Cortot AB, Viteri S, Mazieres J, Smit EF, Thomas M, Iams WT, Cho BC, Kim HR, Yang JC, Chen YM, Patel JD, Bestvina CM, Park K, Griesinger F, Johnson M, Gottfried M, Britschgi C, Heymach J, Sikoglu E, Berghoff K, Schumacher KM, Bruns R, Otto G, Paik PK. 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 Mar 15;28(6):1117 -26. doi: 10.1158/1078-0432.CCR -21 -2733. PMID: 34789481.
Wolf J, Seto T, Han JY, Reguart N, Garon EB, Groen HJM, Tan DSW, Hida T, de Jonge M, Orlov SV, Smit EF, Souquet PJ, Vansteenkiste J, Hochmair M, Felip E, Nishio M, Thomas M, Ohashi K, Toyozawa R, Overbeck TR, de Marinis F, Kim TM, Laack E, Robeva A, Le Mouhaer S, Waldron -Lynch M, San-karan B, Balbin OA, Cui X, Giovannini M, Akimov M, Heist RS; GEOMETRY mono -1 Investigators. Capmatinib in MET Exon 14 -Mutated or MET-Amplified Non -Small -Cell Lung Cancer. N Engl J Med. 2020 Sep 3;383(10):944 -57. doi: 10.1056/NEJMoa2002787. PMID: 32877583.
Nathany, Shrinidhi; Batra, Ullas1,. MET: A narrative review of exon 14 skipping mutation in non -small-cell lung carcinoma. Cancer Research, Statistics, and Treatment: Apr-Jun 2022 – Volume 5 – Issue 2 – p 284 -92.
Wu YL, Cheng Y, Zhou J, Lu S, Zhang Y, Zhao J, Kim DW, Soo RA, Kim SW, Pan H, Chen YM, Chian CF, Liu X, Tan DSW, Bruns R, Straub J, Johne A, Scheele J, Park K, Yang JC; INSIGHT Investigators. Tepotinib plus gefitinib in patients with EGFR-mutant non -small -cell lung cancer with MET over-expression or MET amplification and acquired resistance to previous EGFR inhibitor (INSIGHT study): an open -label, phase 1b/2, multicentre, randomised trial. Lancet Respir Med. 2020 Nov; 8(11):1132 -1143. doi: 10.1016/S2213 -2600(20) 30154 -5. Epub 2020 May 29. Erratum in: Lancet Respir Med. 2020 Jul;8(7):e59. PMID: 32479794.
Oxnard GR, Yang JC, Yu H, Kim SW, Saka H, Horn L, Goto K, Ohe Y, Mann H, Thress KS, Frigault MM, Vishwanathan K, Ghiorghiu D, Ramalingam SS, Ahn MJ. TATTON: a multi -arm, phase Ib trial of osimertinib combined with selumetinib, savolitinib, or durvalumab in EGFR -mutant lung cancer. Ann Oncol. 2020 Apr;31(4):507 -16. doi: 10.1016/j.annonc.2020.01.013. Epub 2020 Jan 24. PMID: 32139298.
F Smit E, Dooms C, Raskin J, Nadal E, Tho LM, Le X, Mazieres J, S Hin H, Morise M, W Zhu V, Tan D, H Holmberg K, Ellers -Lenz B, Adrian S, Brutlach S, Schumacher KM, Karachaliou N, Wu YL. INSIGHT 2: a phase II study of tepotinib plus osimertinib in MET -amplified NSCLC and first -line osimertinib resistance. Future Oncol. 2022 Mar;18(9):1039 -54. doi: 10.2217/fon -2021 -1406. Epub 2021 Dec 17. PMID: 34918545.
Downloads
Published
Issue
Section
License
Copyright (c) 2024 Author(s) (or their employer(s)) and THORAC 2024
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
