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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569583/ https://www.ncbi.nlm.nih.gov/pubmed/34766065 http://dx.doi.org/10.1016/j.jtocrr.2021.100239 |
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author | Yoshimura, Katsuhiro Inoue, Yusuke Inui, Naoki Karayama, Masato Yasui, Hideki Hozumi, Hironao Suzuki, Yuzo Furuhashi, Kazuki Fujisawa, Tomoyuki Enomoto, Noriyuki Nakamura, Yutaro Sugimura, Haruhiko Suda, Takafumi |
author_facet | Yoshimura, Katsuhiro Inoue, Yusuke Inui, Naoki Karayama, Masato Yasui, Hideki Hozumi, Hironao Suzuki, Yuzo Furuhashi, Kazuki Fujisawa, Tomoyuki Enomoto, Noriyuki Nakamura, Yutaro Sugimura, Haruhiko Suda, Takafumi |
author_sort | Yoshimura, Katsuhiro |
collection | PubMed |
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 | Online Article Text |
id | pubmed-8569583 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-85695832021-11-10 MET Amplification and Efficacy of Nivolumab in Patients With NSCLC Yoshimura, Katsuhiro Inoue, Yusuke Inui, Naoki Karayama, Masato Yasui, Hideki Hozumi, Hironao Suzuki, Yuzo Furuhashi, Kazuki Fujisawa, Tomoyuki Enomoto, Noriyuki Nakamura, Yutaro Sugimura, Haruhiko Suda, Takafumi JTO Clin Res Rep Original Article 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. Elsevier 2021-10-08 /pmc/articles/PMC8569583/ /pubmed/34766065 http://dx.doi.org/10.1016/j.jtocrr.2021.100239 Text en © 2021 THE AUTHORS https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Yoshimura, Katsuhiro Inoue, Yusuke Inui, Naoki Karayama, Masato Yasui, Hideki Hozumi, Hironao Suzuki, Yuzo Furuhashi, Kazuki Fujisawa, Tomoyuki Enomoto, Noriyuki Nakamura, Yutaro Sugimura, Haruhiko Suda, Takafumi MET Amplification and Efficacy of Nivolumab in Patients With NSCLC |
title | 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_short | MET Amplification and Efficacy of Nivolumab in Patients With NSCLC |
title_sort | met amplification and efficacy of nivolumab in patients with nsclc |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569583/ https://www.ncbi.nlm.nih.gov/pubmed/34766065 http://dx.doi.org/10.1016/j.jtocrr.2021.100239 |
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