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
Shannon N. Westin, Kathleen N. Moore, Hye Sook Chon, Jung‐Yun Lee, Jessica Thomes Pepin, Michael Sundborg, Ayelet Shai, Joseph de la Garza, Shin Nishio, Michael A. Gold, Ke Wang, Kristi McIntyre, Todd Tillmanns, Stephanie V. Blank, Jihong Liu, Michael McCollum, Fernando Contreras Mejía, Tadaaki Nishikawa, Kathryn P. Pennington, Zoltan Novak, Andréia Cristina de Melo, Jalid Sehouli, Dagmara Klasa-Mazurkiewicz, Christos Papadimitriou, Marta Gil-Martín, Birute Brasiuniene, Conor Donnelly, Paula Michelle del Rosario, Xiaochun Liu, Els Van Nieuwenhuysen, Sophia Frentzas, Ganessan Kichendasse, Bo Gao, Tarek Meniawy, Linda Mileshkin, Gary Richardson, Felicia Roncolato, Jean‐François Baurain, Maryam Bourhaba, Eveline Cuypere, Philip R. Debruyne, Hannelore Denys, Frédéric Forget, Brigitte Honhon, E. Joosens, Els Van Nieuwenhuysen, Vanessa da Costa Miranda, Andréia Cristina de Melo, Joao Daniel Guedes, Charles Andreé Joseph de Pádua, Nicolas Lazaretti, Carolina Martins Vieira, André Mattar, Daniela Neves Palmeiro, Christina Pimentel Oppermann Kussler, Pedro Emanuel Rubini Liedke, João Soares Nunes, Katsuki Arima Tiscoski, Allan Covens, Lara De Guerké, Prafull Ghatage, Lucy Gilbert, Susie Lau, Amit M. Oza, Diane Provencher, Omar Touhami, Congzhu Li, Danbo Wang, Ge Lou, Zhu Genhai, Guiling Li, Shi Hong, Hong Zheng, Wen Hongwu, Jihong Liu, Jing Wang, Ke Wang, Jiang Kui, Li Li, Wang Li, Hao Min, Qi Zhou, Gao Qinglei, Sihai Liao, Zhang Songling, Zhao Weidong, Xiaohua Wu, Wuliang Wang, Rutie Yin, Cheng Ying, Yu Zhang, Liang Zhiqing, Fernando Contreras Mejía, Ángel Luis Martín de Francisco Hernández, Carolina Ortiz Lopez, Carlos Javier Pacheco, Pedro Luis Ramos Guette, Jaime Rendon Pereira, Julian Rivera Diaz, Tomás Sánchez Villegas
Abstract
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.