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
Authors: Westin Shannon N. , Moore Kathleen , Chon Hye Sook , Lee Jung-Yun , Thomes Pepin Jessica , Sundborg Michael , Shai Ayelet , de la Garza Joseph , Nishio Shin , Gold Michael A. , Wang Ke , McIntyre Kristi , Tillmanns Todd D. , Blank Stephanie V. , Liu Ji-Hong , McCollum Michael , Contreras Mejia Fernando , Nishikawa Tadaaki , Pennington Kathryn , Novak Zoltan , De Melo Andreia Cristina , Sehouli Jalid , Klasa-Mazurkiewicz Dagmara , Papadimitriou Christos , Gil-Martin Marta , Brasiuniene Birute , Donnelly Conor , del Rosario Paula Michelle , Liu Xiaochun , Van Nieuwenhuysen Els , Frentzas Sophia , Ganessan Kichendasse , Gao Bo , Meniawy Tarek , Mileshkin Linda , Richardson Gary , Roncolato Felicia , Baurain Jean-Francois , Bourhaba Maryam , De Cuypere Eveline , Debruyne Philip , Denys Hannelore , Forget Frederic , Honhon Brigitte , Joosens Eric , Van Nieuwenhuysen Els , da Costa Miranda Vanessa , De Melo Andreia Cristina , Guedes Joao Daniel , Joseph de Padua Charles Andree , Lazaretti Nicolas , Vieira Carolina Martins , Mattar Andre , Palmeiro Daniela Neves , Oppermann Kussler Christina Pimentel , Rubini Liedke Pedro Emanuel , Nunes Joao Soares , Tiscoski Katsuki Arima , Covens Allan , De Guerke Lara , Ghatage Prafull , Gilbert Lucy , Lau Susie , Oza Amit , Provencher Diane , Touhami Omar , Congzhu Li , Danbo Wang , Ge Lou , Gen-Hai Zhu , Guiling Li , Hong Shi , Hong Zheng , Hongwu Wen , Ji-Hong Liu , Jing Wang , Ke Wang , Kui Jiang , Li Li , Li Wang , Min Hao , Qi Zhou , Qinglei Gao , Sihai Liao , Songling Zhang , Weidong Zhao , Wu Xiaohua , Wuliang Wang , Yin Rutie , Ying Cheng , Yu Zhang , Zhiqing Liang , Mejia Fernando Contreras , Hernandez Angel Luis , Lopez Carolina Ortiz , Pacheco Carlos Javier , Ramos Guette Pedro Luis , Pereira Jaime Rendon , Diaz Julian Rivera , Villegas Tomas Sanchez , Suso Juan Pablo , Torregroza Otero Marco Antonio , Grisan Karin , Vettus Elen , Aktas Bahriye , Egger Eva , Krabisch Petra , Muller Andreas , Rom Joachim , Sehouli Jalid , Sperfeld Antje , Wimberger Pauline , Zorr Andreas , Fountzilas George , Karageorgopoulou Sofia , Papadimitriou Christos , Psyrri Amanda , Zagour Florai , Loen Chan Karen Kar , Ho Wing Ming , Csoszi Tibor , Landherr Laszlo , Novak Zoltan , Papai Zsuzsanna , Poka Robert , Sipocz Istvan , Devinder Paul , Goyal Lovenish , Gupta Sudeep , Naik Radheshyam , Patil Tushar , Somashekhar S.P. , Bruchim Ilan , Kovel Svetlana , Leibovici Anca , Rosengarten Ora , Safra Tamar , Yamagami Wataru , Hamanishi Junzo , Imai Yuichi , Kado Nobuhiro , Kamiura Shoji , Kato Hienori , Kondo Eiji , Kudaka Wataru , Matsumoto Takashi , Mori Masahiko , Nishikawa Tadaaki , Nishio Shin , Okamoto Aikou , Yunokawa Mayu , Sekine Masayuki , Sumi Toshiyuki , Takano Hirokuni , Takehara Kazuhiro , Brasiuniene Birute , Inciura Arturas , Jonuskiene Goda , Cabrera Luviano Jesus Elvis , Dominguez-Andrade Adriana , Gerson-Cwilich Raquel , Hernandez Carlos Hernandez , Hernandez Jesus Lopez , Martinez Lira Jose Luis , Navarrete Aleman Jaime Esteban , Contreras Jessica Reyes , Camargo Vanessa Rosas , Bednarek Wieslawa , Klasa-Mazurkiewicz Dagmara , Kubiatowski Tomasz , Potemski Piotr , Sikorska Magdalena , Chang Suk-Joon , Hong Sook Hee , Kang Sokbom , Kim Byoung-Gie , Kim Jan-Weon , Kim Yong Man , Lee Jung-Yun , Ryu Sang Young , Song Yong Jung , Kirtbaya Dmitriy , Kreynina Julya , Lisyanskaya Alla , Makarova Yulia , Orlova Rashida , Pirmagomedov Albert , Saevets Valeria , Safina Sufia , Skopin Pavel , Tyulyandina Alexandra , Lim Sheow Lei , Su Mien Lynette Ngo , Shao Peng David Tan , Soh Lay Tin , Company Jesus Alarcon , Barretina Pilar , Estevez-Garcia Purificacion , Perez Isaura Fernandez , Galvez Fernando , Garcia Yolanda , Gil-Martin Marta , Martinez Jeronimo , Redondo-Sanchez Andres , Anderson Charles , Berman Tara , Blank Stephanie , Bradley William , Burke James , Cappuccini Fabio , Carney Michael , Chambers Setsuko , Chen Lee-May , Chon Hye Sook , Garza Joseph de la , Depasquale Stephen , DiSilvestro Paul , Edraki Babak , Fleming Evelyn , Fox Jenny , Gold Michael , Gordinier Mary , Guy Michael , Hartenbach Ellen , Haygood Chisten , Jordan Scott , Kilgore Larry , Kim Young , Lucci Joseph , McCollum Michael , Mchale Michael , McIntyre Kristi , Messing Mark , Miller Eirwen , Moore Kathleen , Moroney John , Onstad Michaela , Ortiz Taylor , Ozair Sobia , Pennington Kathryn , Pfaendler Krista , Priebe Anna , Pustilnik Terri , Resnick Kimberly , Rose Peter , Salinas Erin , Sharma Sudarshan , Sobol Urszula , Soliman Pamela , Starks David , Sundborg Michael , Teplinsky Eleonora , Thomes-Pepin Jessica , Tillmanns Todd , Warshal David , Westin Shannon N. , Woliver Thomas 
Published: October 2023

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.