RUBY: dostarlimab with chemotherapy for advanced or recurrent endometrial cancer
Adding the PD-1 antibody dostarlimab to first-line chemotherapy for advanced endometrial cancer cut progression by 72% in tumours with defective mismatch repair and by about a third overall, and later improved survival.
Double-blind, placebo-controlled phase 3 trial of 494 patients with primary advanced (stage III-IV) or first recurrent endometrial cancer randomised to dostarlimab or placebo with carboplatin-paclitaxel for six cycles, then dostarlimab or placebo maintenance for up to three years. Primary endpoints were PFS in the dMMR/MSI-high population and in the overall population, and OS.
In dMMR tumours (about 24% of patients), 24-month PFS was 61.4% vs 15.7% (HR 0.28); overall, 36.1% vs 18.1% (HR 0.64). Overall survival was improved in the whole population (HR 0.69 in the 2024 analysis). Together with NRG-GY018 (pembrolizumab), it made chemo-immunotherapy the first-line standard for advanced endometrial cancer and mismatch repair testing routine.
- dMMR/MSI-high: 24-month PFS 61.4% vs 15.7%; HR 0.28 (95% CI 0.16-0.50).
- Overall population: 24-month PFS 36.1% vs 18.1%; HR 0.64 (95% CI 0.51-0.80).
- Overall survival (Annals of Oncology 2024): HR 0.69 in the overall population; HR 0.32 in dMMR.
- Mismatch-repair-proficient tumours had a smaller benefit (PFS HR about 0.76), concentrated in TP53-mutated and PD-L1-positive subgroups in exploratory analyses.
- Grade 3 or higher adverse events 70.5% vs 59.8%; immune-related events, mainly hypothyroidism and rash, were more frequent with dostarlimab.
Women with newly diagnosed advanced or recurrent endometrial cancer should receive a PD-1 antibody (dostarlimab or pembrolizumab) with their chemotherapy, and mismatch repair testing is now essential because women with dMMR tumours gain a very large and durable benefit. The gain in mismatch-repair-proficient tumours is real but smaller, and molecular classification (POLE, p53, MMR) is increasingly used to decide who benefits most.
- The dMMR benefit dominates; the pMMR benefit is modest and debated for the p53-wild-type, non-specific-molecular-profile subgroup.
- Up to three years of maintenance immunotherapy adds cost and cumulative immune toxicity.
- Recurrent disease after prior adjuvant chemotherapy was included but patients with prior immunotherapy were not.
- The parallel DUO-E trial suggests adding olaparib may help pMMR tumours, but the optimal combination is unsettled.
Pages like this
not linked directly; found by shared links- Key paperKEYNOTE-189: pembrolizumab plus chemotherapy as first treatment for non-squamous lung cancer without a driver mutation
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