{"entity":{"id":"paper-ruby-nejm-2023","kind":"paper","name":"RUBY: dostarlimab with chemotherapy for advanced or recurrent endometrial cancer","aka":[],"tldr":"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.\n\nIn 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.","asOf":"2026-09-08","links":[{"label":"NEJM 2023","url":"https://doi.org/10.1056/NEJMoa2216334"},{"label":"ClinicalTrials.gov NCT03981796","url":"https://clinicaltrials.gov/study/NCT03981796"}],"tags":[],"related":[],"cancers":["endometrial"],"sections":[],"technologies":["checkpoint-inhibitor","cytotoxic-chemotherapy","histopathology-ihc"],"targets":["pd1"],"drugs":["dostarlimab","carboplatin","paclitaxel"],"companies":["gsk"],"institutions":[],"pathways":[],"terms":["msi","pfs","os","first-line"],"trials":[],"people":[],"bottlenecks":["b-immunotherapy-response","b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2216334","authors":"Mirza MR, Chase DM, Slomovitz BM, et al.","paperType":"rct","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."],"whatItMeans":"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."],"changedPractice":true,"participants":494},"route":"/key-papers/paper-ruby-nejm-2023/","neighbours":{"cancer":[{"id":"advanced-recurrent-endometrial-cancer","kind":"cancer","name":"Advanced or recurrent endometrial cancer","route":"/cancers/advanced-recurrent-endometrial-cancer/"},{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"endometrial-mmr-deficient","kind":"cancer","name":"Mismatch-repair-deficient endometrial cancer","route":"/cancers/endometrial-mmr-deficient/"},{"id":"uterine-carcinosarcoma","kind":"cancer","name":"Uterine carcinosarcoma","route":"/cancers/uterine-carcinosarcoma/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"target":[{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"drug":[{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"}],"company":[{"id":"gsk","kind":"company","name":"GSK","route":"/companies/gsk/"}],"term":[{"id":"first-line","kind":"term","name":"Lines of therapy","route":"/terms/first-line/"},{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"},{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"person":[{"id":"mansoor-raza-mirza","kind":"person","name":"Mansoor Raza Mirza","route":"/people/mansoor-raza-mirza/"}]}}