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

Takaomi Hagi, Yukinori Kurokawa, Ryohei Kawabata, Takeshi Omori, Jin Matsuyama, Kazumasa Fujitani, Motohiro Hirao, Yusuke Akamaru, Tsuyoshi Takahashi, Makoto Yamasaki, Taroh Satoh, Hidetoshi Eguchi, Yuichiro Doki, Takaomi Hagi, Yukinori Kurokawa, Ryohei Kawabata, Takeshi Omori, Jin Matsuyama, Kazumasa Fujitani, Motohiro Hirao, Yusuke Akamaru, Tsuyoshi Takahashi, Makoto Yamasaki, Taroh Satoh, Hidetoshi Eguchi, Yuichiro Doki

Abstract

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.

Conflict of interest statement

Y.K. received lecture fees and grant from Ono Pharmaceutical. M.Y. received grant from Ono Pharmaceutical. T.S. received lecture fees from Ono Pharmaceutical and Bristol-Myers Squibb and department support grant from Ono Pharmaceutical. Y.D. received lecture fees and grant from Ono Pharmaceutical.

Figures

Fig. 1. Flow chart of patient eligibility…
Fig. 1. Flow chart of patient eligibility for inclusion in the study.
RR response rate, HPD hyperprogressive disease, CT computed tomography.
Fig. 2. Kaplan–Meier progression-free and overall survivals…
Fig. 2. Kaplan–Meier progression-free and overall survivals for 136 patients who had measurable lesions according to response status.
a Progression-free survival, b overall survival in complete response (CR) or partial response (PR) (n = 25), stable disease (SD) (n = 18), progressive disease (PD) without hyperprogressive disease (HPD) (n = 63) and HPD (n = 30).
Fig. 3. Kaplan–Meier progression-free survival for all…
Fig. 3. Kaplan–Meier progression-free survival for all 200 patients according to PD-L1 and MMR status.
a Tumour-positive score (TPS) <1 (n = 150) or TPS ≥1 (n = 50), b combined positive score (CPS) <1 (n = 83) or ≥1 (n = 117), c CPS <5 (n = 126) or ≥5 (n = 74), d CPS <10 (n = 161) or ≥10 (n = 39) and (e) mismatch repair (MMR) deficient (n = 29) or proficient (n = 171).

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