First-line tepotinib for a very elderly patient with metastatic NSCLC harboring MET exon 14 skipping mutation and high PD-L1 expression

Authors

  • Alessandro Inno Medical Oncology Unit, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar di Valpolicella (VR) - Italy https://orcid.org/0000-0001-6331-6908
  • Giuseppe Bogina Pathology Unit, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar di Valpolicella (VR) - Italy
  • Giulio Settanni Pathology Unit, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar di Valpolicella (VR) - Italy https://orcid.org/0000-0002-8494-226X
  • Matteo Salgarello Nuclear Medicine Unit, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar di Valpolicella (VR) - Italy
  • Giovanni Foti Radiology Unit, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar di Valpolicella (VR) - Italy https://orcid.org/0000-0002-1426-2402
  • Carlo Pomari Pulmonology and Thoracic Endoscopy Unit, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar di Valpolicella (VR) - Italy
  • Vincenzo Picece Medical Oncology Unit, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar di Valpolicella (VR) - Italy
  • Stefania Gori Medical Oncology Unit, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar di Valpolicella (VR) - Italy https://orcid.org/0000-0001-6320-405X

DOI:

https://doi.org/10.33393/dti.2023.2626

Keywords:

Elderly, First-line treatment, MET 14-exon skipping mutation, MET inhibitor, Non-small cell lung cancer, Tepotinib

Abstract

Optimal treatment for metastatic non-small cell lung cancer (NSCLC) with mesenchymal epithelial transition gene (MET) exon 14 skipping mutation has not been established yet. MET inhibitors were demonstrated to be effective and tolerated in patients with this condition, while evidence on safety and efficacy of immunotherapy and/or chemotherapy in this population is limited. Here we report the case of an 86-year-old male with metastatic NSCLC harboring MET exon 14 skipping mutation and with high programmed cell death ligand 1 (PD-L1) expression (tumor proportion score ≥50%). The patient received the MET inhibitor tepotinib as first-line treatment, achieving a partial response, with G2 peripheral edema as adverse event that was successfully managed with temporary discontinuation, dose reduction, diuretics and physical therapy. After 31 months, the patient is still receiving tepotinib, with an ongoing response. Tepotinib is a valuable therapeutic option for first-line treatment of older patients with NSCLC harboring MET exon 14 skipping mutation, even in the presence of high PD-L1 expression.

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References

Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature. 2014;511(7511):543-550. https://doi.org/10.1038/nature13385 PMID:25079552 DOI: https://doi.org/10.1038/nature13385

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. https://doi.org/10.1056/NEJMoa2004407 PMID:32469185 DOI: https://doi.org/10.1056/NEJMoa2004407

Mazieres J, Paik PK, Garassino MC, et al. Tepotinib treatment in patients with MET exon 14-skipping non-small cell lung cancer: long-term follow-up of the VISION phase 2 nonrandomized clinical trial. JAMA Oncol. 2023;e231962. https://doi.org/10.1001/jamaoncol.2023.1962 PMID:37270698 DOI: https://doi.org/10.1001/jamaoncol.2023.1962

European Medicine Agency. Tepmetko. https://www.ema.europa.eu/en/documents/overview/tepmetko-epar-medicine-overview_it.pdf. Accessed October 2022.

U.S. Food and Drug Administration. Tepmekto 2021. www.accessdata.fda.gov/drugsatfda_docs/label/2021/214096s000lbl.pdf. Accessed October 2022.

Reck M, Remon J, Hellmann MD. First-Line immunotherapy for non-small-cell lung cancer. J Clin Oncol. 2022;40(6):586-597. https://doi.org/10.1200/JCO.21.01497 PMID:34985920 DOI: https://doi.org/10.1200/JCO.21.01497

Reck M, Rodríguez-Abreu D, Robinson AG, et al. Five-year outcomes with pembrolizumab versus chemotherapy for metastatic non-small-cell lung cancer with PD-L1 tumor proportion score ≥ 50. J Clin Oncol. 2021;39(21):2339-2349. https://doi.org/10.1200/JCO.21.00174 PMID:33872070 DOI: https://doi.org/10.1200/JCO.21.00174

Jassem J, de Marinis F, Giaccone G, et al. Updated overall survival analysis from IMpower110: atezolizumab versus platinum-based chemotherapy in treatment-naive programmed death-ligand 1-selected NSCLC. J Thorac Oncol. 2021;16(11):1872-1882. https://doi.org/10.1016/j.jtho.2021.06.019 PMID:34265434 DOI: https://doi.org/10.1016/j.jtho.2021.06.019

Sezer A, Kilickap S, Gümüş M, et al. Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet. 2021;397(10274):592-604. https://doi.org/10.1016/S0140-6736(21)00228-2 PMID:33581821 DOI: https://doi.org/10.1016/S0140-6736(21)00228-2

Liu T, Wu S, Fang W, et al. Identifying optimal first-line immune checkpoint inhibitors based regiments for advanced non-small cell lung cancer without oncogenic driver mutations: a systematic review and network meta-analysis. PLoS One. 2023;18(4):e0283719. https://doi.org/10.1371/journal.pone.0283719 PMID:37071610 DOI: https://doi.org/10.1371/journal.pone.0283719

Mazieres J, Drilon A, Lusque A, et al. Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann Oncol. 2019;30(8):1321-1328. https://doi.org/10.1093/annonc/mdz167 PMID:31125062 DOI: https://doi.org/10.1093/annonc/mdz167

Sabari JK, Leonardi GC, Shu CA, et al. 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. https://doi.org/10.1093/annonc/mdy334 PMID:30165371 DOI: https://doi.org/10.1093/annonc/mdy334

Mayenga M, Assié JB, Monnet I, 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;150:21-25. https://doi.org/10.1016/j.lungcan.2020.09.008 PMID:33045465 DOI: https://doi.org/10.1016/j.lungcan.2020.09.008

Guisier F, Dubos-Arvis C, Viñas F, 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;15(4):628-636. https://doi.org/10.1016/j.jtho.2019.12.129 PMID:31945494 DOI: https://doi.org/10.1016/j.jtho.2019.12.129

Schrock AB, Frampton GM, Suh J, et al. Characterization of 298 patients with lung cancer harboring MET exon 14 skipping alterations. J Thorac Oncol. 2016;11(9):1493-1502. https://doi.org/10.1016/j.jtho.2016.06.004 PMID:27343443 DOI: https://doi.org/10.1016/j.jtho.2016.06.004

Akinboro O, Vallejo JJ, Nakajima EC, et al. Outcomes of anti-PD-(L)1 therapy with or without chemotherapy (chemo) for first-line (1L) treatment of advanced non-small cell lung cancer (NSCLC) with PD-L1 score ≥ 50%: FDA pooled analysis. J Clin Oncol. 2022;40:16_suppl, 9000. https://doi.org/10.1200/JCO.2022.40.16_suppl.9000 DOI: https://doi.org/10.1200/JCO.2022.40.16_suppl.9000

Gridelli C, Morabito A, Cavanna L, et al. Cisplatin-based first-line treatment of elderly patients with advanced non-small-cell lung cancer: joint analysis of MILES-3 and MILES-4 phase III trials. J Clin Oncol. 2018;36(25):2585-2592. https://doi.org/10.1200/JCO.2017.76.8390 PMID:30028656 DOI: https://doi.org/10.1200/JCO.2017.76.8390

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. https://doi.org/10.1056/NEJMoa2002787 PMID:32877583 DOI: https://doi.org/10.1056/NEJMoa2002787

Lu S, Fang J, Li X, 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;9(10):1154-1164. https://doi.org/10.1016/S2213-2600(21)00084-9 PMID:34166627 DOI: https://doi.org/10.1016/S2213-2600(21)00084-9

Published

2023-10-06

How to Cite

Inno, A., Bogina, G., Settanni, G., Salgarello, M., Foti, G., Pomari, C., Picece, V., & Gori, S. (2023). First-line tepotinib for a very elderly patient with metastatic NSCLC harboring MET exon 14 skipping mutation and high PD-L1 expression. Drug Target Insights, 17(1), 110–113. https://doi.org/10.33393/dti.2023.2626
Received 2023-07-03
Accepted 2023-09-19
Published 2023-10-06

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