Effectiveness and tolerability of programmed cell death protein-1 inhibitor + chemotherapy compared to chemotherapy for upper gastrointestinal tract cancers

ARTICLE HIGHLIGHTS

Research background

Programmed cell death protein-1 (PD-1) inhibitor has shown effective anti-tumor immune activity by blocking the interaction of PD-1 with programmed death ligand 1 (PD-L1), and it combined with chemotherapy has been approved as a standard first- or second-line treatment option for patients with gastric cancer, gastroesophageal junction (GEJ) cancer and advanced esophageal cancer.

Research motivation

Several clinical trials of PD-1 inhibitors combined with chemotherapy vs chemotherapy alone have been completed or are ongoing. However, in terms of efficacy, it is controversial whether PD-1 inhibitor plus chemotherapy can significantly prolong patients’ overall survival (OS) and progression-free survival (PFS) compared to chemotherapy alone.

Research objectives

To compare the efficacy and safety of PD-1 inhibitor combined with chemotherapy and chemotherapy alone, and provide treatment options for patients with advanced gastric cancer, GEJ cancer and advanced esophageal cancer.

Research methods

We searched PubMed and Embase databases for clinical trials comparing the efficacy and safety of PD-1 inhibitors combined with chemotherapy and chemotherapy alone in gastric cancer, GEJ tumors, and esophageal cancer. The effect value of OS, PFS, objective response rate and adverse events were combined using random or fixed effects models. The significance of the pooled odds ratio or hazard ratio was assessed using the Z-test. We used the χ²-based Q-test and the I² test to evaluate the heterogeneity between studies. Funnel plots were generated to assess the presence of publication bias in the outcomes. Additionally, sensitivity analyses were conducted to assess the stability of the results.

Research results

A total of 9 clinical trials were included in this study. Compared with the chemotherapy group, the PD-1 inhibitor + chemotherapy group had longer OS and PFS, and more patients achieved objective response rates. In addition, the number of adverse reactions in the combined treatment group was higher than that in the chemotherapy group alone. The results of subgroup analysis showed that compared with the subgroup of combined positive score (CPS) ≥ 1, patients in the CPS ≥ 5 and CPS ≥ 10 subgroups were able to achieve better therapeutic outcomes with PD-1 inhibitor combined with chemotherapy.

Research conclusions

The efficacy of PD-1 inhibitor combined with chemotherapy was superior to the chemotherapy group alone in patients with gastric cancer, GEJ tumors, and esophageal cancer. Subgroups with PD-L1 CPS ≥ 5 and ≥ 10 were more likely to benefit from PD-1 inhibitor combined with chemotherapy.

Research perspectives

Our findings provide reference for the treatment of patients with advanced gastric cancer, GEJ tumors, and advanced esophageal cancer. Therefore, our next step is to conduct a randomized controlled trial of PD-1 inhibitors combined with chemotherapy for gastric cancer and GEJ tumors to further improve the management of these patients.