Efficacy comparison of PD-1/PD-L1 inhibitor monotherapy and combination with PARPis or antiangiogenic agents in advanced or recurrent endometrial cancer: a systematic review and network meta-analysis.

Abstract

Purpose: The network meta-analysis (NMA) was aimed to compare and assess the effectiveness of programmed cell death 1 (PD-1)/ programmed cell death ligand 1 (PD-L1) inhibitor monotherapy or combination therapy with other agents for individuals with advanced or recurrent endometrial cancer (EC).

Methods: The NMA was registered on the PROSPERO website (ID: CRD42024545968) and multiple databases were queried to retrieve the articles. It assessed the progression-free survival (PFS) and overall survival (OS) of persons with advanced or recurrent EC, as well as those with deficient mismatch repair (dMMR) and proficient mismatch repair (pMMR) in terms of PFS.

Results: The NMA included 12 studies involving a total of 4,515 patients. Compared to chemotherapy, the PD-1/PD-L1 inhibitor monotherapy (hazard ratio [HR], 0.59; 95% confidence interval [CI]: 0.44-0.78) in PFS, combination therapy with poly (ADP-ribose) polymerase inhibitors (PARPis) (HR, 0.53; 95% CI: 0.32-0.89) or with antiangiogenic agents (HR, 0.48; 95% CI: 0.25-0.83) all showed significant improvements in PFS. PD-1/PD-L1 inhibitor monotherapy resulted in a significantly higher OS (HR, 0.61; 95% CI: 0.37-0.97) compared to chemotherapy. Combination therapy with antiangiogenic agents demonstrated the highest efficacy in extending PFS, while the combination with PARPis had the best performance in extending OS. Patients with dMMR and pMMR subtypes derive greater benefits from PD-1/ PD-L1 inhibitor monotherapy and PD-1/PD-L1 inhibitors combined with PARPis respectively.

Conclusion: Monotherapy with PD-1/PD-L1 inhibitors and combination therapies with PARPis or antiangiogenic agents demonstrate significant potential for individuals with advanced or recurrent EC.