Immune checkpoint inhibitors or targeted therapy by mismatch repair status in endometrial cancer: a meta-analysis

This study evaluated the benefits of immune checkpoint inhibitors (ICIs) and/or targeted therapies in mismatch repair-deficient (dMMR) and mismatch repair-proficient (pMMR) patients with advanced or recurrent endometrial cancer (EC) via network meta-analysis. English databases were searched from inception through January 2025. Randomized controlled trials (RCTs) assessing the efficacy and safety of related therapies for patients with EC stratified by MMR status were included. The main evaluation indicators included progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), and severe adverse events (SAEs). Ten studies were included in the analysis. The results indicated that in the dMMR population, ICIs provide superior survival benefits. Among these, Dostarlimab combined with carboplatin and paclitaxel (CP) had the highest PFS and OS rates. For the pMMR population, Selinexor + CP offers significant benefits over CP alone, although OS outcome data are limited. In pMMR patients with prior chemotherapy, the lenvatinib + pembrolizumab strategy may provide additional PFS benefits relative to chemotherapy treatment. ICIs offered advantages for the dMMR population, whereas selinexor could provide survival benefits for the pMMR population. For pMMR patients who have received prior chemotherapy, the lenvatinib plus pembrolizumab strategy shows promise. Network meta-analysis assessed immune and targeted therapies for advanced/recurrent endometrial cancer patients with dMMR and pMMR statuses. ICIs showed superior survival benefits in dMMR patients, with Dostarlimab + carboplatin and paclitaxel (CP) offering highest PFS and OS rates. Selinexor + CP provided significant benefits for pMMR patients compared with CP alone, although OS data are limited. Lenvatinib + pembrolizumab may offer PFS advantages for pMMR patients with prior chemotherapy. Research suggests that ICIs + chemotherapy benefits patients with dMMR; selinexor + chemotherapy may aid in the development of pMMR.