Recent targeted therapies addition to standard chemotherapy regimen in mismatch repair deficient (Dmmr) primary advanced or recurrent endometrial cancer, to what significance? A network meta-analysis

Endometrial cancer (EC) is one of the most common gynecological cancers, often diagnosed in recurrent or advanced stages. Despite various advances in chemotherapy, high mortality and morbidity persist. Immune checkpoint inhibitors (ICIs) combined with tyrosine kinase inhibitors (TKIs) are recent targeted therapies used alongside chemotherapy in primary advanced or recurrent endometrial cancer, especially in mismatch repair-deficient (dMMR) cases. This study was conducted to compare the use of ICI, TKI, and standard chemotherapy regimens (Carboplatin, Paclitaxel, and/or Doxorubicin) in primary advanced or recurrent endometrial cancer cases with known mismatch repair (MMR) status based on recent evidence. Searching and selection were conducted in adherence to the PRISMA statement across various databases. Inclusion and exclusion criteria were applied. Selected studies were assessed using the Cochrane Risk of Bias 2 (RoB2) tool. Eligible studies were extracted for characteristics and outcomes. The primary outcome of this study was progression-free survival (PFS), with the secondary outcome being overall survival (OS) and adverse events (AEs). Subgroup analysis of mismatch repair deficient (dMMR) and proficient (pMMR) cases was performed. A network meta-analysis was conducted using Review Manager 5.4. Five randomized controlled trials (RCTs) of good quality were included. The analysis found that the ICI plus chemotherapy combination regimen provided better PFS compared to the chemotherapy-only regimen in dMMR-EC subjects (OR = 0.021; 95% CI = 0.003–0.140), but not in pMMR-EC subjects. There was no significant difference in PFS between the ICI plus TKI combination regimen and ICI monotherapy compared to chemotherapy-only. No difference in OS was observed among all groups. Adverse events were higher in the ICI plus chemotherapy combination regimen, but no differences in quality of life or discontinuation rates were noted. ICI plus chemotherapy provided better PFS compared to chemotherapy alone, ICI monotherapy, and ICI plus TKI regimens, respectively in dMMR primary advanced or recurrent endometrial cancer cases. PROSPERO ID: CRD42023472033.