Advertisement

Refining patient selection of MET-activated non-small cell lung cancer through biomarker precision

Published:August 01, 2022DOI:https://doi.org/10.1016/j.ctrv.2022.102444

      Highlights

      • MET exon 14 skipping mutations are a robust biomarker for MET targeted therapies.
      • MET gene copy number gain changes require further validation as a biomarker.
      • Patient selection is crucial in maximizing clinical outcomes of targeted therapies.

      Abstract

      Dysregulated MET signaling plays an important role in lung oncogenesis, tumor growth and invasiveness. It may occur through various mechanisms, such as MET overexpression or gene amplification or mutation, all of which can be detected by specific methods. The utility of MET overexpression as a biomarker remains unclear due to discrepancies in its occurrence and non-standardized cut-off thresholds. MET exon 14 skipping mutation (METex14) was established as a strong predictor of response to selective MET tyrosine kinase inhibitors (TKIs), and clinical trial results in patients with non-small cell lung cancer (NSCLC) harboring METex14 led to the approval of capmatinib and tepotinib by regulatory agencies worldwide. MET amplification is an emerging biomarker, with clinical data indicating an association between MET gene copy number and response to MET-TKIs. Additionally, MET amplification represents an important mechanism of resistance to TKIs in oncogene-driven NSCLC.
      The identification of molecular alterations for which targeted therapies are available is important, and high-throughput next-generation sequencing techniques can provide information on multiple genes at the same time, helping to provide valuable predictive information for oncogene-driven cancers.
      This review summarizes the current methods used for the detection of METex14, MET amplification and MET overexpression, and discusses the evidence for the use of MET-TKIs in patients with NSCLC with MET dysregulation. We discuss the practical challenges that impact the use of METex14 in the clinic and the evidence gaps that need to be addressed to validate additional genomic markers for MET-dependent cancers.

      Keywords

      To read this article in full you will need to make a payment
      ESMO Member Login
      Login with your ESMO username and password.
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Purchase one-time access:

      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Malone E.R.
        • Oliva M.
        • Sabatini P.J.B.
        • Stockley T.L.
        • Siu L.L.
        Molecular profiling for precision cancer therapies.
        Genome Med. 2020; 121: 8
        • Moosavi F.
        • Giovannetti E.
        • Saso L.
        • Firuzi O.
        HGF/MET pathway aberrations as diagnostic, prognostic, and predictive biomarkers in human cancers.
        Crit Rev Clin Lab Sci. 2019; 568: 533-566
        • Recondo G.
        • Che J.
        • Jänne P.A.
        • Awad M.M.
        Targeting MET dysregulation in cancer.
        Cancer Discov. 2020; 107: 922-934
        • Awad M.M.
        • Oxnard G.R.
        • Jackman D.M.
        • Savukoski D.O.
        • Hall D.
        • Shivdasani P.
        • et al.
        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; 347: 721-730
        • Pennacchietti S.
        • Michieli P.
        • Galluzzo M.
        • Mazzone M.
        • Giordano S.
        • Comoglio P.M.
        Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene.
        Cancer Cell. 2003; 34: 347-361
        • Mekki M.S.
        • Mougel A.
        • Vinchent A.
        • Paquet C.
        • Copin M.C.
        • Leroy C.
        • et al.
        Hypoxia leads to decreased autophosphorylation of the MET receptor but promotes its resistance to tyrosine kinase inhibitors.
        Oncotarget. 2018; 943: 27039-27058
        • Garon E.B.
        • Brodrick P.
        Targeted therapy approaches for MET abnormalities in non-small cell lung cancer.
        Drugs. 2021; 815: 547-554
        • Engelman J.A.
        • Zejnullahu K.
        • Mitsudomi T.
        • Song Y.
        • Hyland C.
        • Park J.O.
        • et al.
        MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling.
        Science. 2007; 3165827: 1039-1043
        • Morgillo F.
        • Della Corte C.M.
        • Fasano M.
        • Ciardiello F.
        Mechanisms of resistance to EGFR-targeted drugs: lung cancer.
        ESMO Open. 2016; 13e000060
        • Huang X.
        • Li E.
        • Shen H.
        • Wang X.
        • Tang T.
        • Zhang X.
        • et al.
        Targeting the HGF/MET axis in cancer therapy: Challenges in resistance and opportunities for improvement.
        Front Cell Dev Biol. 2020; 8152: 1-15
        • Shim H.
        Bispecific antibodies and antibody-drug conjugates for cancer therapy: technological considerations.
        Biomolecules. 2020; 103
        • Liang H.
        • Wang M.
        MET oncogene in non-small cell lung cancer: Mechanism of MET dysregulation and agents targeting the HGF/c-Met axis.
        OncoTargets Ther. 2020; : 132491-132510
        • DaSilva J.O.
        • Yang K.
        • Perez Bay A.E.
        • Andreev J.
        • Ngoi P.
        • Pyles E.
        • et al.
        A biparatopic antibody that modulates MET trafficking exhibits enhanced efficacy compared with parental antibodies in MET-driven tumor models.
        Clin Cancer Res. 2020; 266: 1408-1419
      1. Kim J, Park KE, Jeong YS, Kim Y, Park H, Nam JH, et al. Therapeutic efficacy of ABN401, a highly potent and selective MET inhibitor, based on diagnostic biomarker test in MET-addicted cancer. Cancers (Basel) 2020;126.

        • Wolf J.
        • Seto T.
        • Han J.Y.
        • Reguart N.
        • Garon E.B.
        • Groen H.J.M.
        • et al.
        Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer.
        N Engl J Med. 2020; 38310: 944-957
        • Paik P.K.
        • Felip E.
        • Veillon R.
        • Sakai H.
        • Cortot A.B.
        • Garassino M.C.
        • et al.
        Tepotinib in non-small-cell lung cancer with MET exon 14 skipping mutations.
        N Engl J Med. 2020; 38310: 931-943
      2. Guidelines). 2021; https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf
        • Friedlaender A.
        • Drilon A.
        • Banna G.L.
        • Peters S.
        • Addeo A.
        The METeoric rise of MET in lung cancer.
        Cancer. 2020; 12622: 4826-4837
        • Garajová I.
        • Giovannetti E.
        • Biasco G.
        • Peters G.J.
        c-Met as a target for personalized therapy.
        Transl Oncogenomics. 2015;7Suppl 1,; : 13-31
        • Bylicki O.
        • Paleiron N.
        • Assié J.B.
        • Chouaïd C.
        Targeting the MET-signaling pathway in non-small-cell lung cancer: evidence to date.
        Onco Targets Ther. 2020; : 135691-135706
        • Tong J.H.
        • Yeung S.F.
        • Chan A.W.
        • Chung L.Y.
        • Chau S.L.
        • Lung R.W.
        • et al.
        MET amplification and exon 14 splice site mutation define unique molecular subgroups of non-small cell lung carcinoma with poor prognosis.
        Clin Cancer Res. 2016; 2212: 3048-3056
        • Yeung S.F.
        • Tong J.H.M.
        • Law P.P.W.
        • Chung L.Y.
        • Lung R.W.M.
        • Tong C.Y.K.
        • et al.
        Profiling of oncogenic driver events in lung adenocarcinoma revealed MET mutation as independent prognostic factor.
        J Thorac Oncol. 2015; 109: 1292-1300
        • Okuda K.
        • Sasaki H.
        • Yukiue H.
        • Yano M.
        • Fujii Y.
        Met gene copy number predicts the prognosis for completely resected non-small cell lung cancer.
        Cancer Sci. 2008; 9911: 2280-2285
        • Ma P.C.
        • Jagadeeswaran R.
        • Jagadeesh S.
        • Tretiakova M.S.
        • Nallasura V.
        • Fox E.A.
        • et al.
        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; 654: 1479-1488
        • Onozato R.
        • Kosaka T.
        • Kuwano H.
        • Sekido Y.
        • Yatabe Y.
        • Mitsudomi T.
        Activation of MET by gene amplification or by splice mutations deleting the juxtamembrane domain in primary resected lung cancers.
        J Thorac Oncol. 2009; 41: 5-11
        • Frampton G.M.
        • Ali S.M.
        • Rosenzweig M.
        • Chmielecki J.
        • Lu X.
        • Bauer T.M.
        • et al.
        Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors.
        Cancer Discov. 2015; 58: 850-859
        • Schrock A.B.
        • Frampton G.M.
        • Suh J.
        • Chalmers Z.R.
        • Rosenzweig M.
        • Erlich R.L.
        • et al.
        Characterization of 298 patients with lung cancer harboring MET exon 14 skipping alterations.
        J Thorac Oncol. 2016; 119: 1493-1502
        • Liu S.Y.
        • Gou L.Y.
        • Li A.N.
        • Lou N.N.
        • Gao H.F.
        • Su J.
        • et al.
        The unique characteristics of MET exon 14 mutation in chinese patients with NSCLC.
        J Thorac Oncol. 2016; 119: 1503-1510
      3. Pruis MA, Geurts-Giele WRR, von der TJH, Meijssen IC, Dinjens WNM, Aerts J, et al. Highly accurate DNA-based detection and treatment results of MET exon 14 skipping mutations in lung cancer. Lung Cancer 2020;14046-54.

        • Si X.
        • Pan R.
        • Ma S.
        • Li L.
        • Liang L.
        • Zhang P.
        • et al.
        Genomic characteristics of driver genes in Chinese patients with non-small cell lung cancer.
        Thorac Cancer. 2021; 123: 357-363
        • Hur J.Y.
        • Ku B.M.
        • Shim J.H.
        • Jung H.A.
        • Sun J.M.
        • Lee S.H.
        • et al.
        Characteristics and clinical outcomes of non-small cell lung cancer patients in Korea with MET exon 14 skipping.
        In Vivo. 2020; 343: 1399-1406
        • Heist R.S.
        • Shim H.S.
        • Gingipally S.
        • Mino-Kenudson M.
        • Le L.
        • Gainor J.F.
        • et al.
        MET exon 14 skipping in non-small cell lung cancer.
        Oncologist. 2016; 214: 481-486
        • Digumarthy S.R.
        • Mendoza D.P.
        • Zhang E.W.
        • Lennerz J.K.
        • Heist R.S.
        Clinicopathologic and imaging features of non-small-cell lung cancer with MET exon 14 skipping mutations.
        Cancers (Basel). 2019; 1112: 2033
      4. Macari D, Ibironke O, Jinna S, Stender MJ, Jaiyesimi IA. Survival differences between smokers and nonsmokers with EGFR mutated non-small cell lung cancer. J Clin Oncol 2020;3815_suppl:e21509.

        • Gettinger S.
        • Hellmann M.D.
        • Chow L.Q.M.
        • Borghaei H.
        • Antonia S.
        • Brahmer J.R.
        • et al.
        Nivolumab plus erlotinib in patients with EGFR-mutant advanced NSCLC.
        J Thorac Oncol. 2018; 139: 1363-1372
        • Reungwetwattana T.
        • Liang Y.
        • Zhu V.
        • Ou S.I.
        The race to target MET exon 14 skipping alterations in non-small cell lung cancer: the why, the how, the who, the unknown, and the inevitable.
        Lung Cancer. 2017; : 10327-10337
        • 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; 55: 653-663
        • Chan B.A.
        • Hughes B.G.
        Targeted therapy for non-small cell lung cancer: current standards and the promise of the future.
        Transl Lung Cancer Res. 2015; 41: 36-54
        • Champagnac A.
        • Bringuier P.P.
        • Barritault M.
        • Isaac S.
        • Watkin E.
        • Forest F.
        • et al.
        Frequency of MET exon 14 skipping mutations in non-small cell lung cancer according to technical approach in routine diagnosis: results from a real-life cohort of 2,369 patients.
        J Thorac Dis. 2020; 125: 2172-2178
        • Davies K.D.
        • Lomboy A.
        • Lawrence C.A.
        • Yourshaw M.
        • Bocsi G.T.
        • Camidge D.R.
        • et al.
        DNA-based versus RNA-based detection of MET exon 14 skipping events in lung cancer.
        J Thorac Oncol. 2019; 144: 737-741
        • Siravegna G.
        • Mussolin B.
        • Venesio T.
        • Marsoni S.
        • Seoane J.
        • Dive C.
        • et al.
        How liquid biopsies can change clinical practice in oncology.
        Ann Oncol. 2019; 3010: 1580-1590
        • Kilgour E.
        • Rothwell D.G.
        • Brady G.
        • Dive C.
        Liquid biopsy-based biomarkers of treatment response and resistance.
        Cancer Cell. 2020; 374: 485-495
        • Alexander M.
        • Kim S.Y.
        • Cheng H.
        Update 2020: Management of non-small cell lung cancer.
        Lung. 2020; 1986: 897-907
        • Pennell N.A.
        • Arcila M.E.
        • Gandara D.R.
        West H.
        Real-world issues and tough choices. Am Soc Clin Oncol Educ Book, Biomarker testing for patients with advanced non-small cell lung cancer2019: 39531-39542
      5. XALKORI [Prescribing information]. New York, NY: Pfizer; August 2011.

        • Shaw A.T.
        • Ou S.H.I.
        • Bang Y.J.
        • Camidge D.R.
        • Solomon B.J.
        • Salgia R.
        • et al.
        Crizotinib in ROS1-rearranged non-small-cell lung cancer.
        N Engl J Med. 2014; 37121: 1963-1971
        • Shaw A.T.
        • Kim T.M.
        • Crinò L.
        • Gridelli C.
        • Kiura K.
        • Liu G.
        • et al.
        Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial.
        Lancet Oncol. 2017; 187: 874-886
        • Drilon A.
        • Clark J.W.
        • Weiss J.
        • Ou S.I.
        • Camidge D.R.
        • Solomon B.J.
        • et al.
        Antitumor activity of crizotinib in lung cancers harboring a MET exon 14 alteration.
        Nat Med. 2020; 261: 47-51
      6. TABRECTA [Prescribing Information]. East Hanover, NJ: Novartis Phamaceuticals; May 2020.

      7. TEPMETKO [Prescribing information]. Darmstadt: Merck Sharp & Dohme Corp; February 2021.

      8. Heist RS, Garon EB, Tan DS, Groen HJ, Seto T, Smit EF, et al. Accurate detection of MET exon 14 skipping using a liquid biopsy assay in NSCLC patients in the GEOMETRY mono-1 study [abstract PO.CL11.04/4551]. In: Program of the American Association for Cancer Research, Virtual, 17–21 MAy 2021 (https://www.abstractsonline.com/pp8/#!/9325/presentation/4551).

      9. Foundation Medicine. ABRECTA is the first FDA-approved MET inhibitor for patients with metastatic non-small cell lung cancer with MET exon 14 skipping. 2021. (https://www.foundationmedicine.com/press-releases/5112df58-f293-428c-9f50-86abe0911968).

        • Wolf J.
        • Garon E.B.
        • Groen H.J.M.
        • Tan D.S.W.
        • Robeva A.
        • Le Mouhaer S.
        • et al.
        Capmatinib in MET exon 14-mutated, advanced NSCLC: Updated results from the GEOMETRY mono-1 study [abstract 9020].
        J Clin Oncol. 2021; 399020
      10. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN Guidelines) central nervous system cancers. (https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf).

      11. Felip E, Garassino MC, Sakai H, Le X, Veillon R, Smit E, et al. Tepotinib in patients with MET exon 14 (METex14) skipping NSCLC asidentified by liquid (LBx) or tissue (TBx) biopsy [abstract P45.03]. In: Program of the International Association for the Study of Lung Cancer, Virtual, 8–14 September 2021 (https://library.iaslc.org/conference-program?product_id=24&author=felip&category=&date=&session_type=&session=&presentation=&keyword=&cme=undefined&).

        • Paik P.K.
        • Veillon R.
        • Felip E.
        • Cortot A.
        • Sakai H.
        • Mazieres J.
        • et al.
        METex14 ctDNA dynamics & resistance mechanisms detected in liquid biopsy (LBx) from patients (pts) with METex14 skipping NSCLC treated with tepotinib [abstract 9012].
        J Clin Oncol. 2021;3915_suppl.;
        • Patel J.D.
        • Le X.
        • Veillon R.
        • Anderson I.C.
        • Bestvina C.M.
        • Demedts I.
        • et al.
        Intracranial activity of tepotinib in patients (pts) with MET exon 14 (METex14) skipping NSCLC enrolled in VISION [abstract 9084].
        J Clin Oncol. 2021;3915_suppl.;
        • Lu S.
        • Fang J.
        • Li X.
        • Cao L.
        • Zhou J.
        • Guo Q.
        • et al.
        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; 910: 1154-1164
      12. Clinicaltrials.gov. Phase 2 study of glesatinib, sitravatinib or mocetinostat in combination with nivolumab in non-small cell lung cancer. 2021. (https://clinicaltrials.gov/ct2/show/NCT02954991) [accessed May 4, 2021].

        • Salgia R.
        • Sattler M.
        • Scheele J.
        • Stroh C.
        • Felip E.
        The promise of selective MET inhibitors in non-small cell lung cancer with MET exon 14 skipping.
        Cancer Treat Rev. 2020; 87102022
      13. Spira A, Krebs M, Cho BC, Besse B, Goldman J, Janne P, et al. Amivantamab in non-small cell lung cancer (NSCLC) with MET exon 14 skipping (METex14) mutation: initial results from CHRYSALIS. In: Program of the International Association for the Study of Lung Cancer, September 8–14, 2021.

        • Sabari J.K.
        • Leonardi G.C.
        • Shu C.A.
        • Umeton R.
        • Montecalvo J.
        • Ni A.
        • et al.
        PD-L1 expression, tumor mutational burden, and response to immunotherapy in patients with MET exon 14 altered lung cancers.
        Ann Oncol. 2018; 2910: 2085-2091
        • Schoenfeld A.J.
        • Rizvi H.
        • Bandlamudi C.
        • Sauter J.L.
        • Travis W.D.
        • Rekhtman N.
        • et al.
        Clinical and molecular correlates of PD-L1 expression in patients with lung adenocarcinomas.
        Ann Oncol. 2020; 315: 599-608
        • Guisier F.
        • Dubos-Arvis C.
        • Vinas F.
        • Doubre H.
        • Ricordel C.
        • Ropert S.
        • et al.
        Efficacy and safety of anti-PD-1 immunotherapy in patients with advanced NSCLC with BRAF, HER2, or MET mutations or RET translocation: GFPC 01–2018.
        J Thorac Oncol. 2020; 154: 628-636
        • Mazieres J.
        • Drilon A.
        • Lusque A.
        • Mhanna L.
        • Cortot A.B.
        • Mezquita L.
        • et al.
        Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry.
        Ann Oncol. 2019; 308: 1321-1328
        • Baba K.
        • Tanaka H.
        • Sakamoto H.
        • Shiratori T.
        • Tsuchiya J.
        • Ishioka Y.
        • et al.
        Efficacy of pembrolizumab for patients with both high PD-L1 expression and an MET exon 14 skipping mutation: A case report.
        Thorac Cancer. 2019; 102: 369-372
        • Reis H.
        • Metzenmacher M.
        • Goetz M.
        • Savvidou N.
        • Darwiche K.
        • Aigner C.
        • et al.
        MET expression in advanced non-small-cell lung cancer: effect on clinical outcomes of chemotherapy, targeted therapy, and immunotherapy.
        Clin Lung Cancer. 2018; 194: e441-e463
        • Mayenga M.
        • Assie J.B.
        • Monnet I.
        • Massiani M.A.
        • Tabeze L.
        • Friard S.
        • et al.
        Durable responses to immunotherapy of non-small cell lung cancers harboring MET exon-14-skipping mutation: A series of 6 cases.
        Lung Cancer. 2020; : 15021-15025
      14. Awad M. Characterization of 1,387 NSCLCs with MET exon 14 (METex14) skipping alterations (SA) and potential acquired resistance (AR) mechanisms. [abstract 9511]. In: Program of the American Society of Clinical Oncology, 29–31 May 2020.

        • Kato Y.
        • Yamamoto G.
        • Watanabe Y.
        • Yamane Y.
        • Mizutani H.
        • Kurimoto F.
        • et al.
        Long-term efficacy of immune checkpoint inhibitors in non-small cell lung cancer patients harboring MET exon 14 skipping mutations.
        Int J Clin Oncol. 2021; 266: 1065-1072
      15. ClinicalTrials.gov. Safety and efficacy of capmatinib (INC280) plus pembrolizumab vs pembrolizumab alone in NSCLC with PD-L1≥ 50%. 2021. (https://clinicaltrials.gov/ct2/show/record/NCT04139317) [accessed July 9, 2021].

      16. ClinicalTrials.gov. Study of efficacy and safety of nivolumab in combination with EGF816 and of nivolumab in combination with INC280 in patients with previously treated non-small cell lung cancer (EGF816). 2021. (https://clinicaltrials.gov/ct2/show/NCT02323126) [accessed July 9, 2021].

        • Calles A.
        • Riess J.W.
        • Brahmer J.R.
        Checkpoint blockade in lung cancer with driver mutation: Choose the road wisely.
        Am Soc Clin Oncol Educ Book. 2020; : 40372-40384
        • Drilon A.
        • Cappuzzo F.
        • Ou S.I.
        • Camidge D.R.
        Targeting MET in lung cancer: Will expectations finally be met?.
        J Thorac Oncol. 2017; 121: 15-26
        • 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; 179: 569-587
        • Blidner R.A.
        • Haynes B.C.
        • Hyter S.
        • Schmitt S.
        • Pessetto Z.Y.
        • Godwin A.K.
        • et al.
        Design, optimization, and multisite evaluation of a targeted next-generation sequencing assay system for chimeric RNAs from gene fusions and exon-skipping events in non-small cell lung cancer.
        J Mol Diagn. 2019; 212: 352-365
        • Peng L.X.
        • Jie G.L.
        • Li A.N.
        • Liu S.Y.
        • Sun H.
        • Zheng M.M.
        • et al.
        MET amplification identified by next-generation sequencing and its clinical relevance for MET inhibitors.
        Exp Hematol Oncol. 2021; 101: 52
        • Camidge D.R.
        • Otterson G.A.
        • Clark J.W.
        • Ignatius Ou S.H.
        • Weiss J.
        • Ades S.
        • et al.
        Crizotinib in patients with MET-amplified NSCLC.
        J Thorac Oncol. 2021; 166: 1017-1029
        • Schuler M.
        • Berardi R.
        • Lim W.T.
        • de Jonge M.
        • Bauer T.M.
        • Azaro A.
        • et al.
        Molecular correlates of response to capmatinib in advanced non-small-cell lung cancer: clinical and biomarker results from a phase I trial.
        Ann Oncol. 2020; 316: 789-797
        • Sequist L.V.
        • von Pawel J.
        • Garmey E.G.
        • Akerley W.L.
        • Brugger W.
        • Ferrari D.
        • et al.
        Randomized phase II study of erlotinib plus tivantinib versus erlotinib plus placebo in previously treated non-small-cell lung cancer.
        J Clin Oncol. 2011; 2924: 3307-3315
        • Le X.
        • Paz-Ares L.G.
        • Van Meerbeeck J.
        • Viteri S.
        • Galvez C.C.
        • Baz D.V.
        • et al.
        Tepotinib in patients (pts) with advanced non-small cell lung cancer (NSCLC) with MET amplification (METamp) [abstract 9021].
        J Clin Oncol. 2021;3915_suppl.;
      17. ClinicalTrials.gov. Study of telisotuzumab vedotin (ABBV-399) in participants with previously treated c-Met+ non-small cell lung cancer. 2021. (https://clinicaltrials.gov/ct2/show/NCT03539536) [accessed July 9, 2021].

        • Bean J.
        • Brennan C.
        • Shih J.Y.
        • Riely G.
        • Viale A.
        • Wang L.
        • et al.
        MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib.
        Proc Natl Acad Sci USA. 2007; 10452: 20932-20937
        • Kawakami H.
        • Okamoto I.
        • Okamoto W.
        • Tanizaki J.
        • Nakagawa K.
        • Nishio K.
        Targeting MET amplification as a new oncogenic driver.
        Cancers (Basel). 2014; 63: 1540-1552
        • Ko B.
        • He T.
        • Gadgeel S.
        • Halmos B.
        MET/HGF pathway activation as a paradigm of resistance to targeted therapies.
        Ann Transl Med. 2017; 51: 4
        • Xu J.
        • Wang J.
        • Zhang S.
        Mechanisms of resistance to irreversible epidermal growth factor receptor tyrosine kinase inhibitors and therapeutic strategies in non-small cell lung cancer.
        Oncotarget. 2017; 852: 90557-90578
        • Wu Y.L.
        • Cheng Y.
        • Zhou J.
        • Lu S.
        • Zhang Y.
        • Zhao J.
        • et al.
        Tepotinib plus gefitinib in patients with EGFR-mutant non-small-cell lung cancer with MET overexpression 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; 811: 1132-1143
        • Wu Y.L.
        • Zhang L.
        • Kim D.W.
        • Liu X.
        • Lee D.H.
        • Yang J.C.
        • et al.
        Phase Ib/II study of capmatinib (INC280) plus gefitinib after failure of epidermal growth factor receptor (EGFR) inhibitor therapy in patients with EGFR-mutated, MET factor-dysregulated non-small-cell lung cancer.
        J Clin Oncol. 2018; 3631: 3101-3109
      18. ClinicalTrials.gov. Study evaluating efficacy and safety of capmatinib in combination with osimertinib in adult subjects with non-small cell lung cancers as second line therapy (GEOMETRY-E). 2021. (https://clinicaltrials.gov/ct2/show/NCT04816214) [accessed September 30, 2021].

        • Yang J.J.
        • Fang J.
        • Shu Y.Q.
        • Chang J.H.
        • Chen G.Y.
        • He J.X.
        • et al.
        A phase Ib study of the highly selective MET-TKI savolitinib plus gefitinib in patients with EGFR-mutated, MET-amplified advanced non-small-cell lung cancer.
        Invest New Drugs. 2020; 392: 477-487
        • Sequist L.V.
        • Han J.Y.
        • Ahn M.J.
        • Cho B.C.
        • Yu H.
        • Kim S.W.
        • et al.
        Osimertinib plus savolitinib in patients with EGFR mutation-positive, MET-amplified, non-small-cell lung cancer after progression on EGFR tyrosine kinase inhibitors: interim results from a multicentre, open-label, phase 1b study.
        Lancet Oncol. 2020; 213: 373-386
        • Oxnard G.R.
        • Cantarini M.
        • Frewer P.
        • Hawkins G.
        • Peters J.
        • Howarth P.
        • et al.
        A phase II trial of osimertinib plus savolitinib for patients (pts) with EGFR-mutant, MET-driven (MET+), locally advanced or metastatic non-small cell lung cancer (NSCLC), following disease progression on osimertinib [abstract TPS9119].
        J Clin Oncol. 2019;3715_suppl.;
        • Li L.
        • Qu J.
        • Heng J.
        • Zhou C.
        • Xiong Y.
        • Yang H.
        • et al.
        A large real-world study on the effectiveness of the combined inhibition of EGFR and MET in EGFR-mutant advanced non-small cell lung cancer (NSCLC) [abstract 9043].
        J Clin Oncol. 2021;3915_suppl.;
        • Lai G.G.Y.
        • Lim T.H.
        • Lim J.
        • Liew P.J.R.
        • Kwang X.L.
        • Nahar R.
        • et al.
        Clonal MET amplification as a determinant of tyrosine kinase inhibitor resistance in epidermal growth factor receptor-mutant non-small-cell lung cancer.
        J Clin Oncol. 2019; 3711: 876-884
      19. Boni V, Sharma MR, Patnaik A. The resurgence of antibody drug conjugates in cancer therapeutics: Novel targets and payloads. Am Soc Clin Oncol Educ Book. doi:10.1200/edbk_281107 2020:e58-e74.

        • Gymnopoulos M.
        • Betancourt O.
        • Blot V.
        • Fujita R.
        • Galvan D.
        • Lieuw V.
        • et al.
        TR1801-ADC: a highly potent cMet antibody-drug conjugate with high activity in patient-derived xenograft models of solid tumors.
        Mol Oncol. 2020; 141: 54-68
        • Scagliotti G.
        • Moro-Sibilot D.
        • Kollmeier J.
        • Favaretto A.
        • Cho E.K.
        • Grosch H.
        • et al.
        A randomized-controlled phase 2 study of the MET antibody emibetuzumab in combination with erlotinib as first-line treatment for EGFR mutation-positive NSCLC patients.
        J Thorac Oncol. 2020; 151: 80-90
        • Yun J.
        • Lee S.H.
        • Kim S.Y.
        • Jeong S.Y.
        • Kim J.H.
        • Pyo K.H.
        • et al.
        Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR-MET Bispecific Antibody, in Diverse Models of EGFR Exon 20 Insertion-Driven NSCLC.
        Cancer Discov. 2020; 108: 1194-1209
      20. ClinicalTrials.gov. Study of amivantamab, a human bispecific EGFR and cMet antibody, in participants with advanced non-small cell lung cancer (CHRYSALIS). 2021. (https://clinicaltrials.gov/ct2/show/NCT02609776) [accessed April 29, 2021].

        • Haura E.B.
        • Cho B.C.
        • Lee J.S.
        • Han J.Y.
        • Lee K.H.
        • Sanborn R.E.
        • et al.
        JNJ-61186372 (JNJ-372), an EGFR-cMet bispecific antibody, in EGFR-driven advanced non-small cell lung cancer (NSCLC) [abstract 9009].
        J Clin Oncol. 2019;3715_suppl.;
        • Leighl N.B.
        • Shu C.A.
        • Minchom A.
        • Felip E.
        • Cousin S.
        • Cho B.C.
        • et al.
        Amivantamab monotherapy and in combination with lazertinib in post-osimertinib EGFR-mutant NSCLC: Analysis from the CHRYSALIS study [abstract 1192MO].
        In: Program of the European Society for Medical Oncology. 19–Sep 2021 (https://oncologypro.esmo.org/meeting-resources/esmo-congress-2021/amivantamab-plus-lazertinib-in-post-osimertinib-post-platinum-chemotherapy-egfr-mutant-non-small-cell-lung-cancer-nsclc-preliminary-results-fro).
      21. RYBREVANT [Prescribing Information]. Beerse: Janssen Biotech Inc; May 21, 2021.

        • Yang C.Y.
        • Wang L.
        • Sun X.
        • Tang M.
        • Quan H.T.
        • Zhang L.S.
        • et al.
        SHR-A1403, a novel c-Met antibody-drug conjugate, exerts encouraging anti-tumor activity in c-Met-overexpressing models.
        Acta Pharmacol Sin. 2019; 407: 971-979
        • Tong M.
        • Gao M.
        • Xu Y.
        • Fu L.
        • Li Y.
        • Bao X.
        • et al.
        SHR-A1403, a novel c-mesenchymal-epithelial transition factor (c-Met) antibody-drug conjugate, overcomes AZD9291 resistance in non-small cell lung cancer cells overexpressing c-Met.
        Cancer Sci. 2019; 11011: 3584-3594
        • Camidge D.R.
        • Barlesi F.
        • Goldman J.W.
        • Morgensztern D.
        • Heist R.S.
        • Vokes E.E.
        • et al.
        Results of the phase 1b study of ABBV-399 (telisotuzumab vedotin; teliso-v) in combination with erlotinib in patients with c-Met+ non-small cell lung cancer by EGFR mutation status [abstract 3011].
        J Clin Oncol. 2019;3715_suppl.;
      22. ClinicalTrials.gov. Study of capmatinib efficacy in comparison with docetaxel in previously treated participants with non-small cell lung cancer harboring MET exon 14 skipping mutation (GeoMETry-III). 2021. (https://clinicaltrials.gov/ct2/show/study/NCT04427072) [accessed July 9, 2021].

        • Guangzhi M.
        • Yunfu D.
        • Wenjie C.
        • Zhenkun L.
        • Cheng A.
        • Xuebing L.
        • et al.
        The prognostic role of MET protein expression among surgically resected non-small cell lung cancer Patients: a meta-analysis. Frontiers.
        Oncol. 2019; 91441
        • Guo B.
        • Cen H.
        • Tan X.
        • Liu W.
        • Ke Q.
        Prognostic value of MET gene copy number and protein expression in patients with surgically resected non-small cell lung cancer: a meta-analysis of published literatures.
        PLoS One. 2014; 96e99399
        • True L.D.
        Quality control in molecular immunohistochemistry.
        Histochem Cell Biol. 2008; 1303: 473-480
        • Spigel D.R.
        • Ervin T.J.
        • Ramlau R.A.
        • Daniel D.B.
        • Goldschmidt Jr., J.H.
        • Blumenschein Jr, G.R.
        • et al.
        Randomized phase II trial of onartuzumab in combination with erlotinib in patients with advanced non-small-cell lung cancer.
        J Clin Oncol. 2013; 3132: 4105-4114
        • Spigel D.R.
        • Edelman M.J.
        • O'Byrne K.
        • Paz-Ares L.
        • Mocci S.
        • Phan S.
        • et al.
        Results from the phase III randomized trial of onartuzumab plus erlotinib versus erlotinib in previously treated stage IIIB or IV non-small-cell lung cancer: METLung.
        J Clin Oncol. 2017; 354: 412-420
        • Scagliotti G.V.
        • Novello S.
        • Schiller J.H.
        • Hirsh V.
        • Sequist L.V.
        • Soria J.C.
        • et al.
        Rationale and design of MARQUEE: a phase III, randomized, double-blind study of tivantinib plus erlotinib versus placebo plus erlotinib in previously treated patients with locally advanced or metastatic, nonsquamous, non-small-cell lung cancer.
        Clin Lung Cancer. 2012; 135: 391-395
        • Yoshioka H.
        • Azuma K.
        • Yamamoto N.
        • Takahashi T.
        • Nishio M.
        • Katakami N.
        • et al.
        A randomized, double-blind, placebo-controlled, phase III trial of erlotinib with or without a c-Met inhibitor tivantinib (ARQ 197) in Asian patients with previously treated stage IIIB/IV nonsquamous nonsmall-cell lung cancer harboring wild-type epidermal growth factor receptor (ATTENTION study).
        Ann Oncol. 2015; 2610: 2066-2072
      23. Camidge DR, Moiseenko F, Cicin I, Horinouchi H, Filippova E, Bar J, et al. Telisotuzumab vedotin (teliso-v) monotherapy in patients with previously treated c-Met+ advanced non-small cell lung cancer [abstract CT179]. Cancer Res 2021;8113 Supplement.

      24. Colomer R, Mondejar R, Romero-Laorden N, Alfranca A, Sanchez-Madrid F, Quintela-Fandino M. When should we order a next generation sequencing test in a patient with cancer? EClinicalMedicine 2020;25100487.

      25. McKenzie AJ, H HD, Jones SF, Burris H, 3rd. Should next-generation sequencing tests be performed on all cancer patients? Expert Rev Mol Diagn 2019;192:89-93.

        • Pennell N.A.
        • Mutebi A.
        • Zhou Z.Y.
        • Ricculli M.L.
        • Tang W.
        • Wang H.
        • et al.
        Economic impact of next-generation sequencing versus single-gene testing to detect genomic alterations in metastatic non–small-cell lung cancer using a decision analytic model.
        JCO Precision Oncology. 2019; : 31-39
        • Im Y.R.
        • Tsui D.W.Y.
        • Diaz Jr., L.A.
        • Wan J.C.M.
        Next-generation liquid biopsies: Embracing data science in oncology.
        Trends Cancer. 2021; 74: 283-292
        • Gregg J.P.
        • Li T.
        • Yoneda K.Y.
        Molecular testing strategies in non-small cell lung cancer: optimizing the diagnostic journey.
        Transl Lung Cancer Res. 2019; 83: 286-301
        • Elazezy M.
        • Joosse S.A.
        Techniques of using circulating tumor DNA as a liquid biopsy component in cancer management.
        Comput Struct Biotechnol J. 2018; : 16370-16378
        • Felip E.
        • Minotti V.
        • Soo R.
        • Wolf J.
        • Solomon B.
        • Tan D.S.W.
        • et al.
        MET inhibitor capmatinib plus EGFR tyrosine kinase inhibitor nazartinib for EGFR-mutant non-small cell lung cancer [abstract 1284P].
        Ann Oncol. 2020; : 31S829-S30