Dostarlimab + carboplatin/paclitaxel stretches time to next therapy by ≥5 months in frontline advanced endometrial cancer

Dostarlimab, an anti-PD-1 antibody, was paired with standard carboplatin (AUC 5)–paclitaxel (175 mg/m²) for six cycles then continued as Q6-week maintenance in the phase 3 RUBY trial (ENGOT-EN6-NSGO/GOG-3031; NCT03981796) n = 494, 1 L primary advanced/recurrent EC). For 464 patients with advanced or recurrent endometrial cancer,post-hoc analysis shows that median time to first subsequent therapy (TFST) improved to 15.3 mo vs 10.2 mo with placebo-chemo (HR 0.63); time to second subsequent therapy (TSST) lengthened to 31.3 mo vs 19.9 mo (HR 0.67). Benefit deepened in the 11% dMMR/MSI-H subset, where both TFST and TSST were not reached versus 10.5 mo and 24.0 mo on control (HR 0.34 and 0.41). Even in MMR-proficient/MSS disease, TFST gained 2.5 mo and TSST 8.1 mo (HRs 0.73/0.73). These delays build on the previously reported PFS jump from 7–10 mo with chemo alone to 13.1 mo overall and >30 mo in dMMR tumors. Compared with historical carboplatin-paclitaxel TFST roughly mirroring its 10-mo PFS, the dostarlimab regimen halves the pace at which patients need new treatment without added long-term toxicity signals. In the KEYNOTE-868/NRG-GY018 (NCT03914612) trial, the combination of pembrolizumab with carboplatin and paclitaxel as first-line treatment in advanced endometrial cancer demonstrated a 12-month PFS of 74% in the mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) subgroup, and the median TFST was not reached. For the mismatch repair proficient (pMMR) subgroup, the median progression-free survival (mPFS) was 13.1 months with pembrolizumab plus chemotherapy and mTFST was 15.1 months.