Immune checkpoint inhibitors plus chemotherapy in first-line endometrial cancer treatment: Still the era of microsatellites?

Objective: The combination of immune checkpoint inhibitors (ICIs) plus chemotherapy is currently being tested as the first-line treatment of advanced endometrial. We aimed to evaluate the efficacy and safety of this combination. Design: We performed a meta-analysis of randomized clinical trials. Population and setting: Patients with advanced endometrial carcinoma receiving ICIs plus chemotherapy in the experimental arm, compared with chemotherapy plus placebo in the control arm, were included. Methods and Outcomes: We evaluated the progression-free survival (PFS) as an efficacy outcome and the number and grades of adverse events (AEs) for safety. Hazard ratios (HR) for PFS and risk ratios (RR) for AEs, with 95% confidence intervals (CI), were calculated. Results: 1303 patients were treated in the included studies. Adding ICIs to chemotherapy significantly improved PFS in mismatch repair deficient (dMMR—HR 0.29; 95% CI, 0.20–0.42; p < 0.00001) and in mismatch repair proficient (pMMR—HR 0.64; 95% CI, 0.46–0.90; p = 0.01) patients. No difference emerged for all-grades AEs (RR 1.00; p = 0.98), but the risk of ≥G3 AEs was increased in the ICIs + chemotherapy group (RR 1.22; 95% CI, 1.11–1.34; p < 0.0001). Conclusions: Adding ICIs to chemotherapy significantly improves PFS in first-line endometrial cancer, regardless of MMR status.