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Meta-Analysis
. 2020 Oct;9(20):7613-7625.
doi: 10.1002/cam4.3417. Epub 2020 Sep 1.

Efficacy of immune-checkpoint inhibitors in metastatic gastric or gastroesophageal junction adenocarcinoma by patient subgroups: A systematic review and meta-analysis

Yulia Kundel  1   2 , Michal Sternschuss  1   2 , Assaf Moore  1   2 , Gali Perl  1   2 , Baruch Brenner  1   2 , Hadar Goldvaser  1   2
Affiliations
Meta-Analysis

Efficacy of immune-checkpoint inhibitors in metastatic gastric or gastroesophageal junction adenocarcinoma by patient subgroups: A systematic review and meta-analysis

Yulia Kundel et al. Cancer Med. 2020 Oct.

Abstract

Background: Efficacy of immune checkpoint inhibitors (ICIs) in metastatic gastric/gastroesophageal junction (GEJ) adenocarcinoma is inconsistent. Whether the efficacy of ICIs is comparable across different subgroups remains unknown.

Methods: We identified randomized controlled trials (RCTs) that compared standard treatment for metastatic gastric/GEJ adenocarcinoma to ICIs. Hazard ratios (HRs) and 95% confidence intervals (CI) for overall survival (OS) were extracted and pooled in a meta-analysis. Prespecified subgroups were included as follows: age at randomization (</≤65 vs ≥/>65 years), gender (female vs male), ethnicity (Asians vs non-Asians), performance-status (0 vs 1), tumor location (gastric vs GEJ), and histological subtype (diffuse vs others). OS in patients with programmed death ligand (PD-L1) positive and with microsatellite instability-high (MSI-H) were also extracted and pooled in a meta-analysis.

Results: Five RCTs comprising 2,264 patients were analyzed. Compared to standard therapy, ICIs did not improve OS (HR = 0.86, 95% CI 0.71-1.03, P = .10) and the effect of ICIs on OS was similar in all subgroups. Nonsignificantly greater effect sizes were seen in older patients (HR = 0.85 vs 0.88, P = .81), male (HR = 0.82 vs 0.99, P = .16), Asians (HR = 0.86 vs 0.96, P = .55), performance-status 0 (HR = 0.84 vs 0.88, P = .81), GEJ tumors (HR = 0.78 vs 0.90, P = .37), and nondiffuse subtype (HR = 0.71 vs 0.79, P = .62). ICIs were associated with significantly improved OS in patients with MSI-H (HR = 0.33, P = .001), but not in PD-L1 positive disease (HR = 0.86, P = .06).

Conclusions: Compared to standard treatment, ICIs in metastatic gastric/GEJ adenocarcinoma did not improve OS. None of the evaluated subgroups has shown increased magnitude of effect to ICIs, aside of the small group with MSI-H tumors.

Keywords: gastric cancer; gastroesophageal cancer; immune-checkpoint inhibitors; immunotherapy.

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Conflict of interest statement

Dr Moore declared honorarium payment from MSD and Roche, all outside the submitted manuscript. Dr Brenner declared personal speaker and consulting fee from MSD, Roche, BMS, Merck Serono, AbbVie, Boehringer Ingelheim, traveling grants from MSD, Roche, Merck Serono, fees supporting clinical trials and scientific projects from Roche, BMS, Merck Serono, Sanofi, Oncotest‐Teva, all outside the submitted manuscript. Dr Goldvaser declared honorarium payment from Roche, Pfizer, Novartis, Oncotest, all outside the submitted manuscript. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Study selection
Figure 2
Figure 2
Forest plots in the intention to treat population for: (A) Overall‐survival, (B) Progression‐free survival
Figure 3
Figure 3
Forest plots for overall‐survival according to: (A) Ethnicity (Asians vs non‐Asians), (B) Age (≤/<65 vs>/≥65), (C) Gender (female vs male), (D) ECOG performants status (0 vs 1), (E) Primary tumor location (gastric vs GEJ), (F) Histological subtype (Diffuse subtype vs nondiffuse subtype). Hazard ratios for each trial are represented by the squares, the size of the square represents the weight of the trial in the meta‐analysis, and the horizontal line crossing the square represents the 95% confidence interval. The diamonds represent the estimated pooled effect. All P values are two‐sided
Figure 4
Figure 4
Forest plots for OS in: (A) MSI‐H disease, (B) PDL1‐positive disease
See this image and copyright information in PMC

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