MET Amplification and Efficacy of Nivolumab in Patients With NSCLC

Introduction: MET amplification is an important genetic alteration in NSCLC. Unlike in patients with EGFR and ALK alterations, the efficacy of immune checkpoint inhibitors in patients with MET-amplified NSCLC remains unknown. Methods: An exploratory analysis of a prospective, multi-institutional coh...

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Autores principales:	Katsuhiro Yoshimura, MD, PhD, Yusuke Inoue, MD, PhD, Naoki Inui, MD, PhD, Masato Karayama, MD, PhD, Hideki Yasui, MD, PhD, Hironao Hozumi, MD, PhD, Yuzo Suzuki, MD, PhD, Kazuki Furuhashi, MD, PhD, Tomoyuki Fujisawa, MD, PhD, Noriyuki Enomoto, MD, PhD, Yutaro Nakamura, MD, PhD, Haruhiko Sugimura, MD, PhD, Takafumi Suda, MD, PhD
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Lung cancer MET Nivolumab Amplification Immune checkpoint inhibitor Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/5687fa7514e94deaa0cf41bd674bf9fe
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spelling	oai:doaj.org-article:5687fa7514e94deaa0cf41bd674bf9fe2021-12-02T05:03:46ZMET Amplification and Efficacy of Nivolumab in Patients With NSCLC2666-364310.1016/j.jtocrr.2021.100239https://doaj.org/article/5687fa7514e94deaa0cf41bd674bf9fe2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2666364321000989https://doaj.org/toc/2666-3643Introduction: MET amplification is an important genetic alteration in NSCLC. Unlike in patients with EGFR and ALK alterations, the efficacy of immune checkpoint inhibitors in patients with MET-amplified NSCLC remains unknown. Methods: An exploratory analysis of a prospective, multi-institutional cohort comprising 200 patients with advanced or recurrent NSCLC treated with nivolumab monotherapy was performed, and MET amplification was defined as a MET-to-CEP7 ratio of greater than or equal to 2 using fluorescent in situ hybridization. High-level and low-level MET gains were also defined as MET signals ≥10/nuclei and 10> MET signals ≥5/nuclei, respectively. Overall response rates (ORRs) and survival outcomes were evaluated on the basis of the MET gene copy number status. Results: Among 175 patients eligible for analysis, MET amplification was detected in 13 tumors (7.4%). Four (2.3%) high-level and 14 (8.0%) low-level MET gains were also detected. There were no considerable differences in ORRs in accordance with the MET gene copy number status. Similarly, no significant differences in both progression-free survival (PFS) and overall survival (OS) were observed between patients with and without MET-amplified NSCLC (log-rank, p = 0.813 for PFS, and p = 0.855 for OS). Among 101 adenocarcinomas, ORRs in patients with high-level and low-level MET gains (50.0% for both, p = 0.049) were significantly higher than those without MET gains (17.6%), yet survival outcomes for both PFS and OS did not improve. Conclusions: MET amplification was not associated with greater benefit of nivolumab treatment in patients with NSCLC. Further studies are warranted to prioritize immune checkpoint inhibitors in the treatment regimen for patients with MET amplification.Katsuhiro Yoshimura, MD, PhDYusuke Inoue, MD, PhDNaoki Inui, MD, PhDMasato Karayama, MD, PhDHideki Yasui, MD, PhDHironao Hozumi, MD, PhDYuzo Suzuki, MD, PhDKazuki Furuhashi, MD, PhDTomoyuki Fujisawa, MD, PhDNoriyuki Enomoto, MD, PhDYutaro Nakamura, MD, PhDHaruhiko Sugimura, MD, PhDTakafumi Suda, MD, PhDElsevierarticleLung cancerMETNivolumabAmplificationImmune checkpoint inhibitorNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENJTO Clinical and Research Reports, Vol 2, Iss 11, Pp 100239- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Lung cancer MET Nivolumab Amplification Immune checkpoint inhibitor Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Lung cancer MET Nivolumab Amplification Immune checkpoint inhibitor Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Katsuhiro Yoshimura, MD, PhD Yusuke Inoue, MD, PhD Naoki Inui, MD, PhD Masato Karayama, MD, PhD Hideki Yasui, MD, PhD Hironao Hozumi, MD, PhD Yuzo Suzuki, MD, PhD Kazuki Furuhashi, MD, PhD Tomoyuki Fujisawa, MD, PhD Noriyuki Enomoto, MD, PhD Yutaro Nakamura, MD, PhD Haruhiko Sugimura, MD, PhD Takafumi Suda, MD, PhD MET Amplification and Efficacy of Nivolumab in Patients With NSCLC
description	Introduction: MET amplification is an important genetic alteration in NSCLC. Unlike in patients with EGFR and ALK alterations, the efficacy of immune checkpoint inhibitors in patients with MET-amplified NSCLC remains unknown. Methods: An exploratory analysis of a prospective, multi-institutional cohort comprising 200 patients with advanced or recurrent NSCLC treated with nivolumab monotherapy was performed, and MET amplification was defined as a MET-to-CEP7 ratio of greater than or equal to 2 using fluorescent in situ hybridization. High-level and low-level MET gains were also defined as MET signals ≥10/nuclei and 10> MET signals ≥5/nuclei, respectively. Overall response rates (ORRs) and survival outcomes were evaluated on the basis of the MET gene copy number status. Results: Among 175 patients eligible for analysis, MET amplification was detected in 13 tumors (7.4%). Four (2.3%) high-level and 14 (8.0%) low-level MET gains were also detected. There were no considerable differences in ORRs in accordance with the MET gene copy number status. Similarly, no significant differences in both progression-free survival (PFS) and overall survival (OS) were observed between patients with and without MET-amplified NSCLC (log-rank, p = 0.813 for PFS, and p = 0.855 for OS). Among 101 adenocarcinomas, ORRs in patients with high-level and low-level MET gains (50.0% for both, p = 0.049) were significantly higher than those without MET gains (17.6%), yet survival outcomes for both PFS and OS did not improve. Conclusions: MET amplification was not associated with greater benefit of nivolumab treatment in patients with NSCLC. Further studies are warranted to prioritize immune checkpoint inhibitors in the treatment regimen for patients with MET amplification.
format	article
author	Katsuhiro Yoshimura, MD, PhD Yusuke Inoue, MD, PhD Naoki Inui, MD, PhD Masato Karayama, MD, PhD Hideki Yasui, MD, PhD Hironao Hozumi, MD, PhD Yuzo Suzuki, MD, PhD Kazuki Furuhashi, MD, PhD Tomoyuki Fujisawa, MD, PhD Noriyuki Enomoto, MD, PhD Yutaro Nakamura, MD, PhD Haruhiko Sugimura, MD, PhD Takafumi Suda, MD, PhD
author_facet	Katsuhiro Yoshimura, MD, PhD Yusuke Inoue, MD, PhD Naoki Inui, MD, PhD Masato Karayama, MD, PhD Hideki Yasui, MD, PhD Hironao Hozumi, MD, PhD Yuzo Suzuki, MD, PhD Kazuki Furuhashi, MD, PhD Tomoyuki Fujisawa, MD, PhD Noriyuki Enomoto, MD, PhD Yutaro Nakamura, MD, PhD Haruhiko Sugimura, MD, PhD Takafumi Suda, MD, PhD
author_sort	Katsuhiro Yoshimura, MD, PhD
title	MET Amplification and Efficacy of Nivolumab in Patients With NSCLC
title_short	MET Amplification and Efficacy of Nivolumab in Patients With NSCLC
title_full	MET Amplification and Efficacy of Nivolumab in Patients With NSCLC
title_fullStr	MET Amplification and Efficacy of Nivolumab in Patients With NSCLC
title_full_unstemmed	MET Amplification and Efficacy of Nivolumab in Patients With NSCLC
title_sort	met amplification and efficacy of nivolumab in patients with nsclc
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/5687fa7514e94deaa0cf41bd674bf9fe
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MET Amplification and Efficacy of Nivolumab in Patients With NSCLC

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