Author(s): Mansoor R. Mirza, M.D., Dana M. Chase, M.D., Brian M. Slomovitz, M.D., René dePont Christensen, Ph.D., Zoltán Novák, Ph.D., Destin Black, M.D., Lucy Gilbert, M.D., Sudarshan Sharma, M.D., Giorgio Valabrega, M.D., Lisa M. Landrum, M.D., Ph.D., Lars C. Hanker, M.D., Ashley Stuckey, M.D., Ingrid Boere, M.D., Ph.D., Michael A. Gold, M.D., Annika Auranen, M.D., Bhavana Pothuri, M.D., David Cibula, M.D., Carolyn McCourt, M.D., Francesco Raspagliesi, M.D., Mark S. Shahin, M.D., Sarah E. Gill, M.D., Bradley J. Monk, M.D., Joseph Buscema, M.D., Thomas J. Herzog, M.D., Larry J. Copeland, M.D., Min Tian, Ph.D., Zangdong He, Ph.D., Shadi Stevens, M.D., Eleftherios Zografos, M.D., Robert L. Coleman, M.D., and Matthew A. Powell, M.D. for the RUBY Investigators*
Dostarlimab is an immune-checkpoint inhibitor that targets the programmed cell death 1 receptor. The combination of chemotherapy and immunotherapy may have synergistic effects in the treatment of endometrial cancer.
We conducted a phase 3, global, double-blind, randomized, placebo-controlled trial. Eligible patients with primary advanced stage III or IV or first recurrent endometrial cancer were randomly assigned in a 1:1 ratio to receive either dostarlimab (500 mg) or placebo, plus carboplatin (area under the concentration–time curve, 5 mg per milliliter per minute) and paclitaxel (175 mg per square meter of body-surface area), every 3 weeks (six cycles), followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. The primary end points were progression-free survival as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, and overall survival. Safety was also assessed.
Of the 494 patients who underwent randomization, 118 (23.9%) had mismatch repair–deficient (dMMR), microsatellite instability–high (MSI-H) tumors. In the dMMR–MSI-H population, estimated progression-free survival at 24 months was 61.4% (95% confidence interval [CI], 46.3 to 73.4) in the dostarlimab group and 15.7% (95% CI, 7.2 to 27.0) in the placebo group (hazard ratio for progression or death, 0.28; 95% CI, 0.16 to 0.50; P<0.001). In the overall population, progression-free survival at 24 months was 36.1% (95% CI, 29.3 to 42.9) in the dostarlimab group and 18.1% (95% CI, 13.0 to 23.9) in the placebo group (hazard ratio, 0.64; 95% CI, 0.51 to 0.80; P<0.001). Overall survival at 24 months was 71.3% (95% CI, 64.5 to 77.1) with dostarlimab and 56.0% (95% CI, 48.9 to 62.5) with placebo (hazard ratio for death, 0.64; 95% CI, 0.46 to 0.87). The most common adverse events that occurred or worsened during treatment were nausea (53.9% of the patients in the dostarlimab group and 45.9% of those in the placebo group), alopecia (53.5% and 50.0%), and fatigue (51.9% and 54.5%). Severe and serious adverse events were more frequent in the dostarlimab group than in the placebo group.
Dostarlimab plus carboplatin–paclitaxel significantly increased progression-free survival among patients with primary advanced or recurrent endometrial cancer, with a substantial benefit in the dMMR–MSI-H population. (Funded by GSK; RUBY ClinicalTrials.gov number, NCT03981796. opens in new tab.)
Author AffiliationsFrom the Department of Oncology, Rigshospitalet, Copenhagen University Hospital, and the Nordic Society of Gynaecological Oncology–Clinical Trial Unit, Copenhagen (M.R.M.), and the Research Unit for General Practice, University of Southern Denmark, Institute of Public Health, Odense (R.C.) — all in Denmark; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (D.M.C.); the Department of Gynecologic Oncology, Mount Sinai Medical Center, and the Department of Obstetrics and Gynecology, Florida International University, Miami Beach (B.M.S.); the Department of Gynecology, Hungarian National Institute of Oncology, Budapest, Hungary (Z.N.); the Department of Obstetrics and Gynecology, Louisiana State University Health Shreveport, and Willis–Knighton Physician Network, Shreveport (D.B.); the Division of Gynecologic Oncology, McGill University Health Centre, Montreal (L.G.); the Department of Obstetrics and Gynecology, AMITA Adventist Hinsdale Hospital, Hinsdale, IL (S.S.); the University of Turin, A.O. Ordine Mauriziano, Turin (G.V.), and the Gynecologic Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori–Milano, University of Milan, Milan (F.R.) — both in Italy; Indiana University Health Simon Cancer Center, Indianapolis (L.M.L.); the Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany (L.C.H.); Women and Infants Hospital, Providence, RI (A.S.); the Department of Medical Oncology, Erasmus MC Cancer Center, Rotterdam, the Netherlands (I.B.); Oklahoma Cancer Specialists and Research Institute, Tulsa (M.A.G.); Tays Cancer Center and FICAN Mid, Tampere University and Tampere University Hospital, Tampere, Finland (A.A.); New York University Langone Health, New York (B.P.); the Department of Obstetrics and Gynecology, General University Hospital in Prague, First Faculty of Medicine, Charles University, Prague, Czech Republic (D.C.); the Division of Gynecologic Oncology (C.M.) and National Cancer Institute–sponsored NRG Oncology (M.A.P.), Washington University School of Medicine, St. Louis; Hanjani Institute for Gynecologic Oncology, Abington Hospital–Jefferson Health, Asplundh Cancer Pavilion, Sidney Kimmel Medical College, Thomas Jefferson University, Willow Grove (M.S.S.), and GSK, Collegeville (M.T., Z.H.) — both in Pennsylvania; the Division of Gynecologic Oncology, Nancy N. and J.C. Lewis Cancer and Research Pavilion, Savannah, GA (S.E.G.); HonorHealth Research Institute, University of Arizona College of Medicine, and Creighton University School of Medicine, Phoenix (B.J.M.), and the Department of Gynecologic Oncology, Arizona Oncology, Tucson (J.B.); the Department of Obstetrics and Gynecology, University of Cincinnati Cancer Center, Cincinnati (T.J.H.), and Ohio State University Comprehensive Cancer Cen