Efficacy and Safety of PD-1/PD-L1 Inhibitor as Single-Agent Immunotherapy in Endometrial Cancer: A Systematic Review and Meta-Analysis

Abstract

The programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway plays a crucial role in the immune escape mechanism and growth of cancer cells in endometrial cancer (EC). Clinical trials investigating PD-1/PD-L1 inhibitor have shown promising results in other cancers, but their efficacy in EC still remains uncertain. Therefore, this meta-analysis aims to provide an updated and robust analysis of the effectiveness and safety of PD-1/PDL1 inhibitor as single-agent immunotherapy in EC, focusing on the objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). This meta-analysis utilized STATA version 17 and RevMan version 5.4 software to pool the results of relevant studies. Five studies conducted between 2017 and 2022, comprising a total of 480 EC patients enrolled for PD-1/PD-L1 inhibitor immunotherapy met the inclusion criteria. The pooled proportion of EC patients who achieved ORR through PD-1/PD-L1 inhibitor treatment was 26.0% (95% CI: 16.0-36.0%; p < 0.05). Subgroup analysis based on mismatch repair (MMR) status showed an ORR of 44.0% (95% CI: 38.0-50.0%; p = 0.32) for the deficient mismatch repair (dMMR) group and 8.0% (95% CI: 0.0-16.0%; p = 0.07) for the proficient mismatch repair (pMMR) group. Pooled proportion analysis by DCR demonstrated an odds ratio (OR) of 41.0% (95% CI: 36.0-46.0%, p = 0.83) for patients undergoing PD-1/PD-L1 inhibitor treatment. Subgroup analysis based on MMR status revealed DCR of 54.0% (95% CI: 47.0-62.0%; p = 0.83) for the dMMR group, and 31.0% (95% CI: 25.0-39.0%; p = 0.14) for the pMMR group. The efficacy of PD-1/PD-L1 inhibitors was significantly higher in the dMMR group compared to the pMMR group, in terms of both ORR (OR = 6.30; 95% CI = 3.60-11.03; p < 0.05) and DCR (OR = 2.57; 95% CI = 1.66-3.99; p < 0.05). In terms of safety issues, the pooled proportion of patients experiencing at least one adverse event was 69.0% (95% CI: 65.0-73.0%; p > 0.05), with grade three or higher AEs occurring in 16.0% of cases (95% CI: 12.0-19.0%; p > 0.05). Based on the subgroup analysis of MMR status, PD-1/PD-L1 inhibitor immunotherapy showed significantly better efficacy among dMMR patients. These findings suggest that patients with dMMR status may be more suitable for this treatment approach. However, further research on PD-1/PD-L1 inhibitor immunotherapy strategies is needed to fully explore their potential and improve treatment outcomes in EC.

Keywords: adverse events; clinical trials efficacy; endometrial cancer; immune checkpoint inhibitor; mismatch repair; programmed cell death ligand 1; programmed cell death ligand 2; programmed cell death protein 1.

Figure 1

PRISMA flow diagram of study selection and screening [12].

Figure 2

Pooled proportion of ORR for PD-1/PD-L1 inhibitor immunotherapy in endometrial cancer patients [13,14,15,16,17]. Forest plot of (A) overall ORR; (B) ORR with dMMR; (C) ORR with pMMR.

Figure 3

Forest plot of MMR status (dMMR versus pMMR) and ORR for PD-1/PD-L1 inhibitor immunotherapy in endometrial cancer patients [13,14,15].

Figure 4

Pooled proportion of DCR for PD-1/PD-L1 inhibitor immunotherapy in endometrial cancer patients [13,14,15]. Forest plot of (A) overall DCR; (B) DCR with dMMR; (C) DCR with pMMR.

Figure 5

Forest plot of MMR status (dMMR versus pMMR) and DCR for PD-1/PD-L1 inhibitor immunotherapy in endometrial cancer patients [13,14,15].

Figure 6

Pooled proportion of adverse event incidence for PD-1/PD-L1 inhibitor immunotherapy in endometrial cancer patients [14,15,16,17]. Forest plot of (A) overall incidence of adverse events; (B) incidence of adverse events of grade 3 or higher.

Figure 7

Sensitivity analysis of the meta-analysis results using the leave-one-out method [13,14,15,16,17].