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Multicentre biomarker cohort study on the efficacy of nivolumab treatment for gastric cancer

BACKGROUND: Predictive factors of nivolumab treatment response in patients with gastric cancer (GC) remain unclear. METHODS: In this retrospective cohort study, tissue specimens of patients with unresectable or recurrent GC and prior or scheduled treatment with nivolumab as third-line or higher ther...

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Autores principales: Hagi, Takaomi, Kurokawa, Yukinori, Kawabata, Ryohei, Omori, Takeshi, Matsuyama, Jin, Fujitani, Kazumasa, Hirao, Motohiro, Akamaru, Yusuke, Takahashi, Tsuyoshi, Yamasaki, Makoto, Satoh, Taroh, Eguchi, Hidetoshi, Doki, Yuichiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492241/
https://www.ncbi.nlm.nih.gov/pubmed/32616848
http://dx.doi.org/10.1038/s41416-020-0975-7
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author Hagi, Takaomi
Kurokawa, Yukinori
Kawabata, Ryohei
Omori, Takeshi
Matsuyama, Jin
Fujitani, Kazumasa
Hirao, Motohiro
Akamaru, Yusuke
Takahashi, Tsuyoshi
Yamasaki, Makoto
Satoh, Taroh
Eguchi, Hidetoshi
Doki, Yuichiro
author_facet Hagi, Takaomi
Kurokawa, Yukinori
Kawabata, Ryohei
Omori, Takeshi
Matsuyama, Jin
Fujitani, Kazumasa
Hirao, Motohiro
Akamaru, Yusuke
Takahashi, Tsuyoshi
Yamasaki, Makoto
Satoh, Taroh
Eguchi, Hidetoshi
Doki, Yuichiro
author_sort Hagi, Takaomi
collection PubMed
description BACKGROUND: Predictive factors of nivolumab treatment response in patients with gastric cancer (GC) remain unclear. METHODS: In this retrospective cohort study, tissue specimens of patients with unresectable or recurrent GC and prior or scheduled treatment with nivolumab as third-line or higher therapy between September 2017 and February 2019 were collected from 23 institutions. The tumour-positive score (TPS) and combined positive score (CPS) of PD-L1 expression and mismatch repair (MMR) were analysed by immunohistochemistry. Associations between clinicopathological factors and tumour-response rate, hyperprogressive disease (HPD) rate and survival were assessed. RESULTS: Of 200 eligible patients, 143 had measurable lesions. The response and HPD rates were 17.5% and 22.1%, respectively. The response rate was significantly higher in patients with performance status (PS) 0–1 (P = 0.026), non-peritoneal metastasis (P = 0.021), PD-L1 TPS ≥ 1 (P = 0.012), CPS ≥ 5 (P = 0.007) or ≥ 10 (P < 0.001) or MMR deficiency (P < 0.001). The HPD rate was significantly higher in patients with PS 2–3 (P = 0.026), liver metastasis (P < 0.001) and CPS < 10 (P = 0.048). Multivariate analysis revealed that CPS (P = 0.001) and MMR (P = 0.002) were independent prognostic factors of progression-free survival, as well as liver metastasis (P < 0.001), peritoneal metastasis (P = 0.004) and CRP (P < 0.001). CONCLUSIONS: PD-L1 CPS and MMR could be useful biomarkers for nivolumab treatment efficacy in GC. CLINICAL TRIAL REGISTRATION: UMIN000032164.
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spelling pubmed-74922412021-07-03 Multicentre biomarker cohort study on the efficacy of nivolumab treatment for gastric cancer Hagi, Takaomi Kurokawa, Yukinori Kawabata, Ryohei Omori, Takeshi Matsuyama, Jin Fujitani, Kazumasa Hirao, Motohiro Akamaru, Yusuke Takahashi, Tsuyoshi Yamasaki, Makoto Satoh, Taroh Eguchi, Hidetoshi Doki, Yuichiro Br J Cancer Article BACKGROUND: Predictive factors of nivolumab treatment response in patients with gastric cancer (GC) remain unclear. METHODS: In this retrospective cohort study, tissue specimens of patients with unresectable or recurrent GC and prior or scheduled treatment with nivolumab as third-line or higher therapy between September 2017 and February 2019 were collected from 23 institutions. The tumour-positive score (TPS) and combined positive score (CPS) of PD-L1 expression and mismatch repair (MMR) were analysed by immunohistochemistry. Associations between clinicopathological factors and tumour-response rate, hyperprogressive disease (HPD) rate and survival were assessed. RESULTS: Of 200 eligible patients, 143 had measurable lesions. The response and HPD rates were 17.5% and 22.1%, respectively. The response rate was significantly higher in patients with performance status (PS) 0–1 (P = 0.026), non-peritoneal metastasis (P = 0.021), PD-L1 TPS ≥ 1 (P = 0.012), CPS ≥ 5 (P = 0.007) or ≥ 10 (P < 0.001) or MMR deficiency (P < 0.001). The HPD rate was significantly higher in patients with PS 2–3 (P = 0.026), liver metastasis (P < 0.001) and CPS < 10 (P = 0.048). Multivariate analysis revealed that CPS (P = 0.001) and MMR (P = 0.002) were independent prognostic factors of progression-free survival, as well as liver metastasis (P < 0.001), peritoneal metastasis (P = 0.004) and CRP (P < 0.001). CONCLUSIONS: PD-L1 CPS and MMR could be useful biomarkers for nivolumab treatment efficacy in GC. CLINICAL TRIAL REGISTRATION: UMIN000032164. Nature Publishing Group UK 2020-07-03 2020-09-15 /pmc/articles/PMC7492241/ /pubmed/32616848 http://dx.doi.org/10.1038/s41416-020-0975-7 Text en © The Author(s), under exclusive licence to Cancer Research UK 2020 https://creativecommons.org/licenses/by/4.0/Note This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).
spellingShingle Article
Hagi, Takaomi
Kurokawa, Yukinori
Kawabata, Ryohei
Omori, Takeshi
Matsuyama, Jin
Fujitani, Kazumasa
Hirao, Motohiro
Akamaru, Yusuke
Takahashi, Tsuyoshi
Yamasaki, Makoto
Satoh, Taroh
Eguchi, Hidetoshi
Doki, Yuichiro
Multicentre biomarker cohort study on the efficacy of nivolumab treatment for gastric cancer
title Multicentre biomarker cohort study on the efficacy of nivolumab treatment for gastric cancer
title_full Multicentre biomarker cohort study on the efficacy of nivolumab treatment for gastric cancer
title_fullStr Multicentre biomarker cohort study on the efficacy of nivolumab treatment for gastric cancer
title_full_unstemmed Multicentre biomarker cohort study on the efficacy of nivolumab treatment for gastric cancer
title_short Multicentre biomarker cohort study on the efficacy of nivolumab treatment for gastric cancer
title_sort multicentre biomarker cohort study on the efficacy of nivolumab treatment for gastric cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492241/
https://www.ncbi.nlm.nih.gov/pubmed/32616848
http://dx.doi.org/10.1038/s41416-020-0975-7
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