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.

Autor:	Westin SN; University of Texas MD Anderson Cancer Center, Houston, TX., Moore K; Stephenson Cancer Center at the University of Oklahoma Medical Center, Oklahoma, OK., Chon HS; H.Lee Moffitt Cancer Center, Tampa, FL., Lee JY; Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Republic of Korea., Thomes Pepin J; Minnesota Oncology, Minneapolis, MN., Sundborg M; FirstHealth Moore Regional Hospital, Pinehurst, NC., Shai A; RAMBAM Health Care Campus, Haifa, and Israeli Society of Gynecologic Oncology (ISGO), Israel., de la Garza J; Texas Oncology-San Antonio Medical Center, San Antonio, TX., Nishio S; Department of Obstetrics and Gynecology, Kurume University School of Medicine, Kurume, Fukuoka, Japan., Gold MA; Oklahoma Cancer Specialists and Research Institute, Tulsa, OK., Wang K; Tianjin Medical University Cancer Institute & Hospital, Tianjin, China., McIntyre K; Texas Health Presbyterian Hospital, Dallas, TX., Tillmanns TD; West Cancer Center Research Institute & University of Tennessee Health Science Center, Memphis, TN., Blank SV; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, and GOG Foundation (GOG-F), USA., Liu JH; Sun Yat-sen University Cancer Center, Guangzhou, China., McCollum M; Virginia Oncology Associates, Brock Cancer Center, Norfolk, VA, and GOG Foundation (GOG-F), USA., Contreras Mejia F; National Cancer Institute of Colombia, Bogotá, Colombia., Nishikawa T; Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan., Pennington K; Fred Hutchinson Cancer Center, University of Washington Medical Center, Seattle, WA., Novak Z; National Institute of Oncology, Budapest, and Central and Eastern European Gynecologic Oncology Group (CEEGOG), Hungary., De Melo AC; Clinical Research and Technological Development Division, Brazilian National Cancer Institute, Rio de Janeiro, Brazil., Sehouli J; Charité-Department of Gynecology with Center of Oncological Surgery, Universitätsmedizin Berlin, Berlin, and North Eastern German Society of Gynecological Oncology (NOGGO), Germany., Klasa-Mazurkiewicz D; Department of Obstetrics and Gynecology, Gynecological Oncology and Gynecological Endocrinology, Medical University of Gdańsk, Gdańsk, and Polish Gynecologic Oncology Group (PGOG), Poland., Papadimitriou C; Aretaieion University Hospital, National and Kapodistrian University of Athens, Athens, and Hellenic Cooperative Oncology Group (HeCOG), Greece., Gil-Martin M; Medical 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., Brasiuniene B; Department of Medical Oncology, National Cancer Institute of Lithuania, Faculty of Medicine of Vilnius University, Vilnius, and Nordic Society of Gynaecological Oncology (NSGO), Lithuania., Donnelly C; Oncology Biometrics, AstraZeneca, Cambridge, United Kingdom., Del Rosario PM; Oncology R&D, Global Medicines Development, AstraZeneca, Cambridge, United Kingdom., Liu X; Oncology R&D, Late-stage Development, AstraZeneca, Gaithersburg, MD., Van Nieuwenhuysen E; University Hospital Leuven, Leuven, and Luxembourg Gynaecological Oncology Group (BGOG), Belgium.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2024 Jan 20; Vol. 42 (3), pp. 283-299. Date of Electronic Publication: 2023 Oct 21.
DOI:	10.1200/JCO.23.02132
Abstrakt:	Purpose: 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. Methods: 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. Results: 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. Conclusion: 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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu