Abstract

Background

Clinicopathological and molecular features of responders to nivolumab for advanced gastric cancer (AGC) are not well understood.

Methods

Patients (pts) with AGC who were treated with nivolumab after two or more chemotherapy regimens in a single institution from September 2017 to May 2018 were enrolled in this study. PD-L1 expression in tumor cells (TC) and mismatch repair (MMR) were analyzed by immunohistochemistry. Epstein-Barr virus (EBV) was detected by in situ hybridization. Cancer genome alterations were evaluated by a next-generation sequencing-based panel. High tumor mutation burden (TMB) was defined as more than 10 mutations/megabase.

Results

A total of 80 pts were analyzed in this study. Tumor response was evaluated in 72 pts with measurable lesions and 14 pts (19%) had an objective response. Overall response rate (ORR) was significantly higher in pts with ECOGPS 0 in those with PS 1 or 2, MMR-deficient (MMR-D) in those with MMR-proficient (MMR-P), PD-L1+ in TC in those with PD-L1- in TC and PIK3CA mutation in those with PIK3CA wild-type. ORR was 31% in pts with at least one of the following factors; MMR-D, high TMB, EBV+ and PD-L1+ in TC vs. 0% in those without these factors. Progression-free survival was significantly longer in pts with PS 0 than in those with PS 1 or 2, MMR-D than in those with MMR-P, and PD-L1+ in TC than in those with PD-L1- in TC.

Conclusions

Some features were associated with favorable response to nivolumab for AGC. Combining these features might be useful to predict efficacy.

Details

Title
Clinicopathological and molecular features of responders to nivolumab for patients with advanced gastric cancer
Author
Mishima, Saori; Kawazoe, Akihito; Nakamura, Yoshiaki; Sasaki, Akinori; Kotani, Daisuke; Kuboki, Yasutoshi; Bando, Hideaki; Kojima, Takashi; Doi, Toshihiko; Ohtsu, Atsushi; Yoshino, Takayuki; Kuwata, Takeshi; Tsuji, Akihito; Shitara, Kohei
Section
Research Article
Publication year
2019
Publication date
Jan 2019
Publisher
BMJ Publishing Group LTD
e-ISSN
20511426
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1186/s40425-019-0514-3
ProQuest document ID
2638109601
Copyright
© 2019 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.