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(The University of Texas MD Anderson Cancer Center), Kathleen N. Moore(University of Oklahoma Medical Center), Hye Sook Chon(Moffitt Cancer Center), Jung‐Yun Lee(Yonsei University), Jessica Thomes Pepin(Minnesota Oncology), Michael Sundborg(FirstHealth of the Carolinas), Ayelet Shai(Rambam Health Care Campus), Joseph de la Garza(Texas Oncology), Shin Nishio(Kurume University), Michael A. Gold(Oklahoma Cancer Specialists and Research Institute), Ke Wang(Tianjin Medical University Cancer Institute and Hospital), Kristi McIntyre(University of Tennessee Health Science Center), Todd Tillmanns(Gynecologic Oncology Group), Stephanie V. Blank(Gynecologic Oncology Group), Jihong Liu(Gynecologic Oncology Group), Michael McCollum(Gynecologic Oncology Group), Fernando Contreras Mejía(Instituto Nacional de Cancerología), Tadaaki Nishikawa(University of Washington Medical Center), Kathryn P. Pennington(University of Washington Medical Center), Zoltan Novak(National Institute of Oncology), Andréia Cristina de Melo(Instituto Nacional de Câncer - INCA), Jalid Sehouli(Nord-Ostdeutsche Gesellschaft für Gynäkologische Onkologie), Dagmara Klasa-Mazurkiewicz(National and Kapodistrian University of Athens), Christos Papadimitriou(National and Kapodistrian University of Athens), Marta Gil-Martín(Vilnius University), Birute Brasiuniene(AstraZeneca (United Kingdom)), Conor Donnelly(AstraZeneca (United Kingdom)), Paula Michelle del Rosario(AstraZeneca (United Kingdom)), Xiaochun Liu(The European Academy of Gynaecological Surgery), Els Van Nieuwenhuysen(The University of Texas MD Anderson Cancer Center), Sophia Frentzas(The University of Texas MD Anderson Cancer Center), Ganessan Kichendasse(The University of Texas MD Anderson Cancer Center), Bo Gao(The University of Texas MD Anderson Cancer Center), Tarek Meniawy(The University of Texas MD Anderson Cancer Center), Linda Mileshkin(The University of Texas MD Anderson Cancer Center), Gary Richardson(The University of Texas MD Anderson Cancer Center), Felicia Roncolato(The University of Texas MD Anderson Cancer Center), Jean‐François Baurain(The University of Texas MD Anderson Cancer Center), Maryam Bourhaba(The University of Texas MD Anderson Cancer Center), Eveline Cuypere(The University of Texas MD Anderson Cancer Center), Philip R. Debruyne(The University of Texas MD Anderson Cancer Center), Hannelore Denys(The University of Texas MD Anderson Cancer Center), Frédéric Forget(The University of Texas MD Anderson Cancer Center), Brigitte Honhon(The University of Texas MD Anderson Cancer Center), E. Joosens(The European Academy of Gynaecological Surgery), Els Van Nieuwenhuysen(The University of Texas MD Anderson Cancer Center), Vanessa da Costa Miranda(Instituto Nacional de Câncer - INCA), Andréia Cristina de Melo(The University of Texas MD Anderson Cancer Center), Joao Daniel Guedes(The University of Texas MD Anderson Cancer Center), Charles Andreé Joseph de Pádua(The University of Texas MD Anderson Cancer Center), Nicolas Lazaretti(The University of Texas MD Anderson Cancer Center), Carolina Martins Vieira(The University of Texas MD Anderson Cancer Center), André Mattar(The University of Texas MD Anderson Cancer Center), Daniela Neves Palmeiro(The University of Texas MD Anderson Cancer Center), Christina Pimentel Oppermann Kussler(The University of Texas MD Anderson Cancer Center), Pedro Emanuel Rubini Liedke(The University of Texas MD Anderson Cancer Center), João Soares Nunes(The University of Texas MD Anderson Cancer Center), Katsuki Arima Tiscoski(The University of Texas MD Anderson Cancer Center), Allan Covens(The University of Texas MD Anderson Cancer Center), Lara De Guerké(The University of Texas MD Anderson Cancer Center), Prafull Ghatage(The University of Texas MD Anderson Cancer Center), Lucy Gilbert(The University of Texas MD Anderson Cancer Center), Susie Lau(The University of Texas MD Anderson Cancer Center), Amit M. Oza(The University of Texas MD Anderson Cancer Center), Diane Provencher(The University of Texas MD Anderson Cancer Center), Omar Touhami(The University of Texas MD Anderson Cancer Center), Congzhu Li(The University of Texas MD Anderson Cancer Center), Danbo Wang(The University of Texas MD Anderson Cancer Center), Ge Lou(The University of Texas MD Anderson Cancer Center), Zhu Genhai(The University of Texas MD Anderson Cancer Center), Guiling Li(The University of Texas MD Anderson Cancer Center), Shi Hong(The University of Texas MD Anderson Cancer Center), Hong Zheng(The University of Texas MD Anderson Cancer Center), Wen Hongwu(Sun Yat-sen University), Jihong Liu(The University of Texas MD Anderson Cancer Center), Jing Wang(The University of Texas MD Anderson Cancer Center), Ke Wang(The University of Texas MD Anderson Cancer Center), Jiang Kui(The University of Texas MD Anderson Cancer Center), Li Li(The University of Texas MD Anderson Cancer Center), Wang Li(The University of Texas MD Anderson Cancer Center), Hao Min(The University of Texas MD Anderson Cancer Center), Qi Zhou(The University of Texas MD Anderson Cancer Center), Gao Qinglei(The University of Texas MD Anderson Cancer Center), Sihai Liao(The University of Texas MD Anderson Cancer Center), Zhang Songling(The University of Texas MD Anderson Cancer Center), Zhao Weidong(The University of Texas MD Anderson Cancer Center), Xiaohua Wu(The University of Texas MD Anderson Cancer Center), Wuliang Wang(The University of Texas MD Anderson Cancer Center), Rutie Yin(The University of Texas MD Anderson Cancer Center), Cheng Ying(The University of Texas MD Anderson Cancer Center), Yu Zhang(The University of Texas MD Anderson Cancer Center), Liang Zhiqing(The University of Texas MD Anderson Cancer Center), Fernando Contreras Mejía(Instituto Nacional de Cancerología), 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, Juan Pablo Suso, Marco Antonio Torregroza Otero, Karin Grišan, Elen Vettus, Bahriye Aktas, Eva K. Egger, Petra Krabisch, Andreas Müller, Joachim Rom(Nord-Ostdeutsche Gesellschaft für Gynäkologische Onkologie), Jalid Sehouli(Nord-Ostdeutsche Gesellschaft für Gynäkologische Onkologie), Antje Sperfeld, Pauline Wimberger, Andreas Zorr, George Fountzilas, Sofia Karageorgopoulou(National and Kapodistrian University of Athens), Christos Papadimitriou(National and Kapodistrian University of Athens), Amanda Psyrri, Florai Zagour, Karen K. L. Chan(The University of Texas MD Anderson Cancer Center), Wing Ming Ho, Tibor Csőszi, László Landherr(National Institute of Oncology), Zoltan Novak(National Institute of Oncology), Zsuzsanna Pápai, Ròbert Póka, István Sipőcz(The University of Texas MD Anderson Cancer Center), Paul Devinder, Lovenish Goyal, Sudeep Gupta, Radheshyam Naik, Tushar Patil(The University of Texas MD Anderson Cancer Center), S. P. Somashekhar, Ilan Bruchim, Svetlana Kovel, Anca Leibovici(The University of Texas MD Anderson Cancer Center), Ora Rosengarten, Tamar Safra, Wataru Yamagami, Junzo Hamanishi, Yuichi Imai, Nobuhiro Kado, Shoji Kamiura, H. Kato, Eiji Kondo, Wataru Kudaka, Takashi Matsumoto, Masahiko Mori(National Cancer Center Hospital East), Tadaaki Nishikawa(Kurume University), Shin Nishio(Kurume University), Aikou Okamoto, Mayu Yunokawa, Masayuki Sekine, Toshiyuki Sumi, Hirokuni Takano, Kazuhiro Takehara(Vilnius University), Birute Brasiuniene(Vilnius University), Arturas Inčiūra, Goda Jonuškienė, Jesus Elvis Cabrera Luviano, Adriana Domínguez-Andrade, Raquel Gerson-Cwilich, Carlos Hernández Hernández, Jesus Lopez Hernandez, Jose Luis Martinez Lira, Jaime Esteban Navarrete Aleman(The University of Texas MD Anderson Cancer Center), Jessica Reyes Contreras, Vanessa Rosas Camargo(The University of Texas MD Anderson Cancer Center), Wiesława Bednarek(Gdańsk Medical University), Dagmara Klasa-Mazurkiewicz(The University of Texas MD Anderson Cancer Center), Tomasz Kubiatowski(The University of Texas MD Anderson Cancer Center), Piotr Potemski(The University of Texas MD Anderson Cancer Center), Magdalena Sikorska(The University of Texas MD Anderson Cancer Center), Suk‐Joon Chang(The University of Texas MD Anderson Cancer Center), Sook Hee Hong(The University of Texas MD Anderson Cancer Center), Sokbom Kang(The University of Texas MD Anderson Cancer Center), Byoung‐Gie Kim(The University of Texas MD Anderson Cancer Center), J. Kim(The University of Texas MD Anderson Cancer Center), Yong‐Man Kim(Yonsei University), Jung-Yun Lee(The University of Texas MD Anderson Cancer Center), Sang Young Ryu(The University of Texas MD Anderson Cancer Center), Yong Jung Song(The University of Texas MD Anderson Cancer Center), Dmitriy Kirtbaya(The University of Texas MD Anderson Cancer Center), Julya M. Kreynina(The University of Texas MD Anderson Cancer Center), Alla Lisyanskaya(The University of Texas MD Anderson Cancer Center), Yulia Makarova(The University of Texas MD Anderson Cancer Center), Р. В. Орлова(The University of Texas MD Anderson Cancer Center), Albert Pirmagomedov(The University of Texas MD Anderson Cancer Center), Valeria Saevets(The University of Texas MD Anderson Cancer Center), Sufia Safina(The University of Texas MD Anderson Cancer Center), Pavel Skopin(The University of Texas MD Anderson Cancer Center), Alexandra Tyulyandina(The University of Texas MD Anderson Cancer Center), Sheow Lei Lim, Lynette Ngo Su Mien, David Peng(The University of Texas MD Anderson Cancer Center), Lay Tin Soh(The University of Texas MD Anderson Cancer Center), Maria-Pilar Barretina-Ginesta(The University of Texas MD Anderson Cancer Center), Purificación Estévez-García(The University of Texas MD Anderson Cancer Center), Isaura Fernández Pérez(The University of Texas MD Anderson Cancer Center), Fernando Gálvez(The University of Texas MD Anderson Cancer Center), Yolanda García García(The University of Texas MD Anderson Cancer Center), Marta Gil-Martín(Institut d'Investigació Biomédica de Bellvitge), Jerónimo Martínez(The University of Texas MD Anderson Cancer Center), Andres Redondo-Sanchez(The University of Texas MD Anderson Cancer Center), Charles Anderson(The University of Texas MD Anderson Cancer Center), Tara Berman(The University of Texas MD Anderson Cancer Center), Stephanie V. Blank(Gynecologic Oncology Group), William E. Bradley(The University of Texas MD Anderson Cancer Center), James Burke(The University of Texas MD Anderson Cancer Center), Fabio Cappuccini(The University of Texas MD Anderson Cancer Center), Michael E. Carney(The University of Texas MD Anderson Cancer Center), Setsuko K. Chambers(The University of Texas MD Anderson Cancer Center), Lee-may Chen(The University of Texas MD Anderson Cancer Center), Hye Sook Chon(The University of Texas MD Anderson Cancer Center), Joseph de la Garza(Texas Oncology), Stephen DePasquale(The University of Texas MD Anderson Cancer Center), Paul DiSilvestro(The University of Texas MD Anderson Cancer Center), Babak Edraki(The University of Texas MD Anderson Cancer Center), Evelyn Fleming(The University of Texas MD Anderson Cancer Center), Jenny R. Fox(The University of Texas MD Anderson Cancer Center), Michael A. Gold(Oklahoma Cancer Specialists and Research Institute), Mary E. Gordinier(The University of Texas MD Anderson Cancer Center), Michael S. Guy(The University of Texas MD Anderson Cancer Center), Ellen M. Hartenbach(The University of Texas MD Anderson Cancer Center), Chisten Haygood(The University of Texas MD Anderson Cancer Center), Scott Jordan(The University of Texas MD Anderson Cancer Center), Larry C. Kilgore(The University of Texas MD Anderson Cancer Center), Young Kim(The University of Texas MD Anderson Cancer Center), Joseph A. Lucci(The University of Texas MD Anderson Cancer Center), Michael McCollum(Gynecologic Oncology Group), Michael Mchale(The University of Texas MD Anderson Cancer Center), Kristi McIntyre(Texas Health Dallas), Mark Messing(The University of Texas MD Anderson Cancer Center), Eirwen M. Miller(The University of Texas MD Anderson Cancer Center), Kathleen N. Moore(University of Oklahoma Medical Center), John W. Moroney(The University of Texas MD Anderson Cancer Center), Michaela Onstad(The University of Texas MD Anderson Cancer Center), Taylor M. Ortiz(The University of Texas MD Anderson Cancer Center), Sobia Ozair(The University of Texas MD Anderson Cancer Center), Kathryn P. Pennington(University of Washington Medical Center), Krista S. Pfaendler(The University of Texas MD Anderson Cancer Center), Anna Priebe(The University of Texas MD Anderson Cancer Center), Terri Pustilnik(The University of Texas MD Anderson Cancer Center), Kimberly Resnick(The University of Texas MD Anderson Cancer Center), Peter G. Rose(The University of Texas MD Anderson Cancer Center), E. Salinas(The University of Texas MD Anderson Cancer Center), Sudarshan Sharma(The University of Texas MD Anderson Cancer Center), Urszula Sobol(The University of Texas MD Anderson Cancer Center), Pamela T. Soliman(The University of Texas MD Anderson Cancer Center), David Starks(The University of Texas MD Anderson Cancer Center), Michael Sundborg(FirstHealth of the Carolinas), Eleonora Teplinsky(The University of Texas MD Anderson Cancer Center), Jessica Thomes-Pepin(Minnesota Oncology), Todd Tillmanns(University of Tennessee Health Science Center), David Warshal(The University of Texas MD Anderson Cancer Center), Shannon N. Westin(The University of Texas MD Anderson Cancer Center), Thomas Woliver
Cited by 307Open Access
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.
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