# RUBY: dostarlimab with chemotherapy for advanced or recurrent endometrial cancer

Source: https://onco.cc/key-papers/paper-ruby-nejm-2023/  
OnCo record `paper-ruby-nejm-2023` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2023
- DOI: 10.1056/NEJMoa2216334
- Authors: Mirza MR, Chase DM, Slomovitz BM, et al.
- Findings: 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.
- What it means: 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.
- Caveats: 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.

## Sources

- NEJM 2023: https://doi.org/10.1056/NEJMoa2216334
- ClinicalTrials.gov NCT03981796: https://clinicaltrials.gov/study/NCT03981796

## Connected records

- cancers: [Advanced or recurrent endometrial cancer](https://onco.cc/cancers/advanced-recurrent-endometrial-cancer/), [Endometrial cancer](https://onco.cc/cancers/endometrial/), [Mismatch-repair-deficient endometrial cancer](https://onco.cc/cancers/endometrial-mmr-deficient/), [Uterine carcinosarcoma](https://onco.cc/cancers/uterine-carcinosarcoma/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- targets: [PD-1](https://onco.cc/targets/pd1/)
- drugs: [Carboplatin](https://onco.cc/drugs/carboplatin/), [Dostarlimab](https://onco.cc/drugs/dostarlimab/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/)
- companies: [GSK](https://onco.cc/companies/gsk/)
- terms: [Lines of therapy](https://onco.cc/terms/first-line/), [Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)](https://onco.cc/terms/msi/), [Overall survival (OS)](https://onco.cc/terms/os/), [Progression-free survival (PFS)](https://onco.cc/terms/pfs/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [No one can predict who responds to immunotherapy](https://onco.cc/bottlenecks/b-immunotherapy-response/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- people: [Mansoor Raza Mirza](https://onco.cc/people/mansoor-raza-mirza/)

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