2025-03-13 国立がん研究センター
<関連情報>
- https://www.ncc.go.jp/jp/information/researchtopics/2025/0313/index.html
- https://www.ncc.go.jp/jp/information/researchtopics/2025/0313/20250313.pdf
- https://www.nature.com/articles/s41591-025-03575-0
胃食道癌におけるニボルマブと化学療法またはイピリムマブの併用:無作為化第3相試験の探索的バイオマーカー解析 Nivolumab plus chemotherapy or ipilimumab in gastroesophageal cancer: exploratory biomarker analyses of a randomized phase 3 trial
Kohei Shitara,Yelena Y. Janjigian,Jaffer Ajani,Markus Moehler,Jin Yao,Xuya Wang,Aparna Chhibber,Dimple Pandya,Lin Shen,Marcelo Garrido,Carlos Gallardo,Lucjan Wyrwicz,Kensei Yamaguchi,Tomasz Skoczylas,Arinilda Bragagnoli,Tianshu Liu,Michael Schenker,Patricio Yañez,Ruben Kowalyszyn,Michalis Karamouzis,Thomas Zander,Kynan Feeney,Elena Elimova,Parul Doshi,… Ming Lei
Nature Medicine Published:07 March 2025
DOI:https://doi.org/10.1038/s41591-025-03575-0
Abstract
First-line nivolumab-plus-chemotherapy demonstrated superior overall survival (OS) and progression-free survival versus chemotherapy for advanced gastroesophageal adenocarcinoma with programmed death ligand 1 combined positive score ≥ 5, meeting both primary end points of the randomized phase 3 CheckMate 649 trial. Nivolumab-plus-ipilimumab provided durable responses and higher survival rates versus chemotherapy; however, the prespecified OS significance boundary was not met. To identify biomarkers predictive of differential efficacy outcomes, post hoc exploratory analyses were performed using whole-exome sequencing and RNA sequencing. Nivolumab-based therapies demonstrated improved efficacy versus chemotherapy in hypermutated and, to a lesser degree, Epstein–Barr virus-positive tumors compared with chromosomally unstable and genomically stable tumors. Within the KRAS-altered subgroup, only patients treated with nivolumab-plus-chemotherapy demonstrated improved OS benefit versus chemotherapy. Low stroma gene expression signature scores were associated with OS benefit with nivolumab-based regimens; high regulatory T cell signatures were associated with OS benefit only with nivolumab-plus-ipilimumab. Our analyses suggest that distinct and overlapping pathways contribute to the efficacy of nivolumab-based regimens in gastroesophageal adenocarcinoma.
