Immune checkpoint inhibitor plus chemotherapy versus chemotherapy alone in HER2-negative advanced gastric or gastroesophageal junction cancer: A systematic review and meta-analysis of randomized controlled trials.

Abstract

e16052 Background: Synergistic effects of immune checkpoint inhibitors (ICI) and chemotherapy (CTX) have been documented, demonstrating promising efficacy across diverse cancer types. This report presents a meta-analysis aimed at assessing the effectiveness and safety profile of ICI plus CTX in patients diagnosed with Human Epidermal Growth Factor Receptor type 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) cancers. Methods: PubMed, EMBASE, Cochrane Central, and ASCO Abstracts databases were systematically searched for randomized controlled trials comparing PD-1 or PD-L1 inhibitors plus CTX with CTX alone in patients diagnosed with HER2-negative gastric or GEJ cancers. The assessed outcomes included Progression-Free Survival (PFS) and Overall Survival (OS), stratified by PD-L1 Combinated Positive Score (CPS) in tumors, as well as any Adverse Events (AE) and Treatment-Related Adverse Events (TRAE) graded as ≥ 3. Statistical analysis employed a random effects model in R version 4.3.2, with heterogeneity assessed using the I2 statistic. Results: We conducted a meta-analysis comprising 6 RCTs involving 5,520 patients, among whom 2,766 received PD-1 or PD-L1 inhibitors in combination with chemotherapy. This combined regimen demonstrated significant improvements in both general PFS (HR 0.73; 95% CI [0.68; 0.78]; p < 0.01) and OS (HR 0.77; 95% CI [0.71; 0.84]; p < 0.01). Specifically, the combination of ICI with CTX exhibited enhanced PFS across various subgroups, including CPS ≥ 5 (HR 0.66; 95% CI [0.59; 0.75]; p < 0.01), CPS ≥ 10 (HR 0.75; 95% CI [0.65; 0.87]; p < 0.01), and CPS ≤ 1 (HR 0.75; 95% CI [0.69; 0.82]; p < 0.01). Median OS similarly reflected this improvement in CPS ≥ 5 (HR 0.71; 95% CI [0.63; 0.81]; p < 0.01) and CPS ≥ 10 (HR 0.66; 95% CI [0.57; 0.75]; p < 0.01) subgroups, albeit not in the CPS ≤ 1 subgroup (HR 0.91; 95% CI [0.77; 1.08]; p = 0.29). Furthermore, no significant differences were observed in the incidence of adverse events (AE) (RR 1.01; 95% CI [0.99; 1.04]; p = 0.221), while grade 3 or more treatment-related adverse events (TRAE) were slightly higher in the ICI plus CTX group (RR 1.15; 95% CI [1.01; 1.32]; p = 0.038). Conclusions: These findings indicate that the combination of ICI with CTX demonstrates superior efficacy compared to CTX alone in HER2-negative gastric or GEJ cancer. However, this efficacy trend is not maintained in patients with PD-L1 CPS ≤ 1 tumors. Moreover, the absence of differences in AE and the slight increase in TRAE in the ICI plus CTX group still further supports the safety profile of this combination therapy.