An observational study of the effectiveness and safety of nivolumab plus chemotherapy for untreated advanced or recurrent gastric cancer in Japanese real-world settings: the G-KNIGHT study

Abstract

Background: Nivolumab plus chemotherapy has shown efficacy in clinical trials for advanced or recurrent gastric cancer (GC). However, real-world utilization data are limited. In this study, we aimed to assess the effectiveness, safety, and treatment status of first line nivolumab plus chemotherapy in Japanese patients with treatment-naïve advanced or recurrent GC.

Methods: Untreated patients with advanced or recurrent GC who initiated nivolumab plus chemotherapy as first line treatment from November 2021 to June 2023 across 23 Japanese sites were enrolled in this observational study (G-KNIGHT). This report focused on the objective response rate (ORR), real-world progression-free survival (rwPFS), and the treatment-related adverse event (TRAE) incidence. Furthermore, subgroup analyses for ORR and rwPFS were conducted for patients stratified by various factors including age and the programmed cell death ligand 1 (PD-L1) combined positive score (CPS).

Results: Among 527 patients (median age, 70.3 years; 25.2% aged ≥ 75 years; 65.5% male; 84.3% with advanced GC), the median follow-up period was 10.4 (interquartile range, 6.7-15.2) months. The ORR was 65.6% (95% confidence interval [CI], 59.9-70.9%). The median rwPFS (months, 95% CI) was 6.9 (6.2-7.6); by subgroups: age < 75 years, 6.7 (6.0-7.5); age ≥ 75 years, 7.4 (6.2-8.6); PD-L1 CPS < 1, 7.5 (6.5-9.0); CPS 1-5, 6.2 (5.5-8.0); and CPS ≥ 5, 7.0 (6.2-8.2). TRAEs occurred in 91.3% of patients, with 40.4% experiencing grade ≥ 3 events.

Conclusions: This large-scale real-world study supports the effectiveness and safety of nivolumab plus chemotherapy in untreated Japanese patients with advanced or recurrent GC.

Keywords: Japan; Nivolumab; Observational study; Stomach neoplasms.

Fig. 1

Effectiveness outcomes a DOR, b rwPFS*, and c OS *One patient without available data on the date of confirmed rwPFS after nivolumab initiation was excluded from the analysis. Abbreviations: CI, confidence interval; DOR, duration of response; OS, overall survival; rwPFS, real-world progression-free survival

Fig. 2

ORR by subgroup ORR was analyzed in patients with measurable disease and response evaluation, which were assessed by investigators per Response Evaluation Criteria in Solid Tumors v1.1. *MSI-low is not shown because only one patient was applicable. Abbreviations: BOR, best overall response; CI, confidence interval; CPS, combined positive score; CR, complete response; DCR, disease control rate; MSI, microsatellite instability; MSS, microsatellite stability; ORR, objective response rate; PD, progressive disease; PD-L1, programmed cell death ligand 1; PR, partial response; SD, stable disease

Fig. 3

rwPFS* by subgroups a Age (< 75 and ≥ 75 years), b ECOG PS (0, 1, and ≥ 2), c PD-L1 CPS^† (< 1, 1–5, and ≥ 5), d PD-L1 CPS^† (< 5 and ≥ 5), e MSI status^‡ (MSS and MSI-H), f peritoneal dissemination (without and with), g ascites in patients with peritoneal dissemination^§ (without, mild to moderate, and massive), h liver metastasis (without and with), and i lymph node metastasis (without and with). *One patient without available data on the date of confirmed rwPFS after nivolumab initiation was excluded from the analysis. ^†Seventy-nine patients without available PD-L1 CPS data were excluded from the analysis. ^‡A total of 319 patients without available MSI data were excluded from the analysis. MSI-L is not shown because only 3 patients were applicable. ^§Twenty-eight patients with ascites whose ascites severity was unknown were excluded from the analysis. Abbreviations: CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; CPS, combined positive score; MSI, microsatellite instability; MSS, microsatellite stability; PD-L1, programmed cell death ligand 1; rwPFS, real-world progression-free survival; MSI, microsatellite instability