Efficacy and safety of anti-PD-1/PD-L1 agents vs chemotherapy in patients with gastric or gastroesophageal junction cancer: a systematic review and meta-analysis

Abstract

Background: Current therapeutic options have limited efficacy for patients with advanced gastric or gastroesophageal junction cancer. Immune checkpoint inhibition now has been increasingly used in advanced gastric or gastroesophageal junction cancer therapy. To further understand the efficacy and safety of anti-programmed cell death 1 (PD-1) and its ligand 1 (PD-L1) agents is critical for clinical practice. We conducted this systematic review and meta-analysis to assess the benefit and risk of PD-1 and PD-L1 inhibitors.

Methods: The PubMed, EMBASE, Cochrane Library, and Web of Science online databases were searched up to Jun 16, 2019. Primary outcomes were overall survival (OS), progression-free survival (PFS). Second outcomes were objective response rate (ORR), disease control rate (DCR) and adverse events.

Results: Six studies were assessed for inclusion in the final synthesis, of which 5 were eligible for meta-analysis. Compared with chemotherapy, the pooled hazard ratio (HR) for OS and PFS was, respectively, 1.01 (95% confidence interval [CI]: 0.88-1.15, P = .93) and 1.58 (95% CI: 1.38-1.81, P < .001) after treatment with PD-1/PD-L1 inhibitors. In patients treated with anti-PD-1/PD-L1 agents, the pooled ORR was 9.9% (95% CI: 4.4%-15.5%) and the pooled DCR was 30.8% (95% CI: 21.8%-39.9%). Sub-analysis for treatment related adverse events indicated that fatigue was the most common toxicity in anti-PD-1/PD-L1 therapy (incidence 10.6%, 95% CI: 5.6%-15.6%).

Conclusion: PD-1/PD-L1 inhibitors appear to improve the antitumor activity in advanced gastric or gastroesophageal junction cancer patients. However, single-agent PD-1/PD-L1 inhibitor did not result in a relative improvement in OS and PFS compared with chemotherapy in the treatment of patients with advanced gastric or gastroesophageal junction cancer. Further randomized clinical trials are warranted to confirm our findings.

Figure 1

Flow chart of the study identification process.

Figure 2

Forest plots of hazard ratios for overall survival in patients with gastric or gastroesophageal junction cancer between PD-1/PD-L1 inhibitor group and chemotherapy group. CI = confidence interval, I2 = index of heterogeneity, IV = Inverse Variance statistical method, Fix = Fixed effect analysis model.

Figure 3

Forest plots of hazard ratios for progression-free survival in patients with gastric or gastroesophageal junction cancer between PD-1/PD-L1 inhibitor group and chemotherapy group.