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

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

doi:10.1038/s41416-020-0975-7

Abstract

BackgroundPredictive factors of nivolumab treatment response in patients with gastric cancer (GC) remain unclear.MethodsIn 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.ResultsOf 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).ConclusionsPD-L1 CPS and MMR could be useful biomarkers for nivolumab treatment efficacy in GC.Clinical trial registrationUMIN000032164.

Highlights

Predictive factors of nivolumab treatment response in patients with gastric cancer (GC) remain unclear
Among 205 GC patients who were enrolled in this study, five were ineligible, for the following reasons: four did not receive nivolumab treatment and one demonstrated metachronous malignancy
Of the 200 patients who were eligible for study inclusion, 143 had measurable lesions, while 57 did not, and the proportions of patients with specific programmed death-ligand 1 (PD-L1) expression statuses were as follows: tumour-positive score (TPS) ≥ 1, 25.0%; combined positive score (CPS) ≥ 1, 58.5%; CPS ≥ 5, 37.0%; CPS ≥ 10, 19.5%

Summary

Introduction

Predictive factors of nivolumab treatment response in patients with gastric cancer (GC) remain unclear. 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). Several studies revealed that paradoxical accelerated tumour progression, known as hyperprogressive disease (HPD), was observed in some patients after initiation of therapy with antibodies against PD-1 or programmed death-ligand 1 (PD-L1).[11,12,13] Taken together, it is necessary to identify precise predictive biomarkers to determine which patients will exhibit positive or negative effects following PD-1 blockade

Methods

Results

Conclusion