Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial

Author(s): Shannon N. Westin, MD, MPH1; Kathleen Moore, MD2; Hye Sook Chon, MD3; Jung-Yun Lee, MD4; Jessica Thomes Pepin, MD5; Michael Sundborg, MD6; Ayelet Shai, MD, PhD7; Joseph de la Garza, MD8; Shin Nishio, MD9; Michael A. Gold, MD10; Ke Wang, MD11; Kristi McIntyre, MD12; Todd D. Tillmanns, MD13; Stephanie V. Blank, MD14; Ji-Hong Liu, MD15; Michael McCollum, MD16; Fernando Contreras Mejia, MD17; Tadaaki Nishikawa, MD18; Kathryn Pennington, MD19; Zoltan Novak, MD, PhD20; Andreia Cristina De Melo, MD21; Jalid Sehouli, MD22; Dagmara Klasa-Mazurkiewicz, MD23; Christos Papadimitriou, MD24; Marta Gil-Martin, MD25; Birute Brasiuniene, MD, PhD26; Conor Donnelly, PhD27; Paula Michelle del Rosario, MD28; Xiaochun Liu, MD, PhD29; Els Van Nieuwenhuysen, MD30
Source: https://doi.org/10.1200/JCO.23.02132
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

Initial results from the DUO-E study in metastatic endometrial cancer. The preliminary report suggests that maintenance durvalumab and maintenance durvalumab + olaparib were superior to standard observation after systemic carbo/taxol. As the trial data matures, the question will be: is this in all patients or driven by those with dMMR or HDR mutations?


Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)–deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease.


This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control.


Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1–positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents.


Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer.

Author Affiliations

1University of Texas MD Anderson Cancer Center, Houston, TX; 2Stephenson Cancer Center at the University of Oklahoma Medical Center, Oklahoma, OK; 3H.Lee Moffitt Cancer Center, Tampa, FL; 4Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Republic of Korea; 5Minnesota Oncology, Minneapolis, MN; 6FirstHealth Moore Regional Hospital, Pinehurst, NC; 7RAMBAM Health Care Campus, Haifa, and Israeli Society of Gynecologic Oncology (ISGO), Israel; 8Texas Oncology-San Antonio Medical Center, San Antonio, TX; 9Department of Obstetrics and Gynecology, Kurume University School of Medicine, Kurume, Fukuoka, Japan; 10Oklahoma Cancer Specialists and Research Institute, Tulsa, OK; 11Tianjin Medical University Cancer Institute & Hospital, Tianjin, China; 12Texas Health Presbyterian Hospital, Dallas, TX; 13West Cancer Center Research Institute & University of Tennessee Health Science Center, Memphis, TN; 14Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, and GOG Foundation (GOG-F), USA; 15Sun Yat-sen University Cancer Center, Guangzhou, China; 16Virginia Oncology Associates, Brock Cancer Center, Norfolk, VA, and GOG Foundation (GOG-F), USA; 17National Cancer Institute of Colombia, Bogotá, Colombia; 18Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan; 19Fred Hutchinson Cancer Center, University of Washington Medical Center, Seattle, WA; 20National Institute of Oncology, Budapest, and Central and Eastern European Gynecologic Oncology Group (CEEGOG), Hungary; 21Clinical Research and Technological Development Division, Brazilian National Cancer Institute, Rio de Janeiro, Brazil; 22Charité—Department of Gynecology with Center of Oncological Surgery, Universitätsmedizin Berlin, Berlin, and North Eastern German Society of Gynecological Oncology (NOGGO), Germany; 23Department of Obstetrics and Gynecology, Gynecological Oncology and Gynecological Endocrinology, Medical University of Gdańsk, Gdańsk, and Polish Gynecologic Oncology Group (PGOG), Poland; 24Aretaieion University Hospital, National and Kapodistrian University of Athens, Athens, and Hellenic Cooperative Oncology Group (HeCOG), Greece; 25Medical Oncology Department, Catalan Institute of Oncology-Institut d’Investigació Biomédica de Bellvitge (IDIBELL), Hospital Duran i Reynals, L’Hospitalet-Barcelona, Barcelona, and Grupo Español de Investigación en Cáncer de Ovario (GEICO), Spain; 26Department of Medical Oncology, National Cancer Institute of Lithuania, Faculty of Medicine of Vilnius University, Vilnius, and Nordic Society of Gynaecological Oncology (NSGO), Lithuania; 27Oncology Biometrics, AstraZeneca, Cambridge, United Kingdom; 28Oncology R&D, Global Medicines Development, AstraZeneca, Cambridge, United Kingdom; 29Oncology R&D, Late-stage Development, AstraZeneca, Gaithersburg, MD; 30University Hospital Leuven, Leuven, and Luxembourg Gynaecological Oncology Group (BGOG), Belgium

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