First-line immunotherapy strategies in pMMR advanced endometrial cancer: A network meta-analysis.

e17650 Background: Optimal first-line treatment for mismatch repair–proficient (pMMR) advanced or recurrent endometrial cancer remains uncertain in the setting of multiple emerging immunotherapy-based regimens. We conducted a network meta-analysis to compare chemotherapy-based versus chemotherapy-free immunotherapy strategies. Methods: We performed a frequentist network meta-analysis of randomized controlled trials evaluating first-line systemic therapy in primary advanced or recurrent pMMR endometrial cancer using the R-based NetMetaEasy tool. Progression-free survival (PFS) hazard ratios (HRs) were synthesized using a random-effects model, with carboplatin–paclitaxel (TC) as the common comparator. Strategies included TC plus pembrolizumab, dostarlimab, durvalumab, atezolizumab, durvalumab plus olaparib, dostarlimab plus niraparib, and lenvatinib plus pembrolizumab. Results: Seven randomized trials comprising eight treatment strategies were included. Chemotherapy-based immunotherapy combinations improved PFS compared with TC alone, whereas the chemotherapy-free regimen lenvatinib plus pembrolizumab did not. Significant PFS benefit versus TC was observed for TC plus pembrolizumab (HR 0.54, 95% CI 0.41–0.71), TC plus durvalumab with olaparib (HR 0.57, 95% CI 0.44–0.73), TC plus dostarlimab with niraparib (HR 0.63, 95% CI 0.44–0.91), TC plus dostarlimab (HR 0.76, 95% CI 0.59–0.98), and TC plus durvalumab (HR 0.77, 95% CI 0.61–0.98). No significant benefit was observed with TC plus atezolizumab (HR 0.92, 95% CI 0.73–1.16) or lenvatinib plus pembrolizumab (HR 0.99, 95% CI 0.81–1.20). Network estimates favored TC plus pembrolizumab over lenvatinib plus pembrolizumab (HR 0.55, 95% CI 0.39–0.76). P-score ranking identified TC plus pembrolizumab (0.90) and TC plus durvalumab with olaparib (0.85) as top regimens. Conclusions: In pMMR advanced endometrial cancer, first-line immunotherapy strategies incorporating chemotherapy provide the greatest PFS benefit within available randomized evidence. Chemotherapy-free immunotherapy did not improve outcomes versus standard chemotherapy, supporting chemotherapy-based immunotherapy as the preferred first-line approach.