Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer

著者: Charles E. Geyer, Judy E. Garber, Richard D. Gelber, Greg Yothers, Manuel Taboada, L. Ross, Priya Rastogi, Karen Cui, Amal Arahmani, Gursel Aktan, Anne Armstrong, Mónica Arnedos, Judith Balmaña, Jonas Bergh, Judith M. Bliss, Suzette Delaloge, Susan M. Domchek, Andrea Eisen, F. Elsafy, L.E. Fein, Anitra Fielding, James M. Ford, Sue Friedman, Karen A. Gelmon, Luca Gianni, Michael Gnant, Simon J. Hollingsworth, Seock‐Ah Im, Agnes Jager, Oskar T. Johannsson, Sunil R. Lakhani, W Janni, Barbro Linderholm, T.-W. Liu, Niklas Loman, Larissa A. Korde, Sibylle Loibl, Peter C. Lucas, Frederik Marmé, E. Martinez de Dueñas, Robin McConnell, Kelly‐Anne Phillips, Martine Piccart, Giovanna Rossi, Rita K. Schmutzler, Elżbieta Senkus, Zhi-Ming Shao, Priyanka Sharma, Christian F. Singer, Tanja Španić, Elmar Stickeler, Masakazu Toi, Tiffany A. Traina, Giuseppe Viale, Gabriele Zoppoli, Y.H. Park, Rinat Yerushalmi, Huan Yang, D. Pang, Kyung Hae Jung, Audrey Mailliez, Zhaoqing Fan, Isabelle Tennevet, J. Zhang, T. Nagy, Gabe S. Sonke, Qiuhong Sun, Marina Parton, Marco Colleoni, Marcus Schmidt, Adam Brufsky, W. Razaq, Bella Kaufman, David Cameron, Christine Campbell, Andrew Tutt, P. Sevelda, Ferdinand Haslbauer, Monika Penzinger, Leopold Öhler, Christoph Tinchon, Richard Greil, Sonja Heibl, Rupert Bartsch, Viktor Wette, Christian F. Singer, Claudia Pasterk, Ruth Helfgott, Gunda Pristauz-Telsnigg, Herbert Stöger, A. Weltermann, Daniel Egle, I. Thiel, David Fuchs, Holger Rumpold, Kathrin Strasser‐Weippl, Beate Rautenberg, Volkmar Müller, Marcus Schmidt, Stefan Paepke, Mustafa Aydoğdu, Christoph Thomssen, Joachim Rom, Christine Mau, Peter A. Fasching, Uwe-Jochen Göhring, Thorsten Kühn, S Noeding, Sherko Kümmel, John Hackmann, Elmar Stickeler, Abhishek Joshi, Joanna Dewar, Michael Friedländer, Kelly‐Anne Phillips, Yoland Antill, Natasha Woodward, Ehtesham Abdi, Susan Tiley, Mathew George, David Boadle, Annabel Goodwin, André van der Westhuizen, George Kannourakis, N. Murray, Nicole McCarthy, Judith R. Kroep, Maaike de Boer, Joan B. Heijns, Agnes Jager, Franciscus Erdkamp, Sandra D. Bakker, Gabe S. Sonke, Amer Sami, John M. Mackey, Catherine Prady, Andrea Eisen, Christine Desbiens, Érica Patocskai, Cristiano Ferrario, Karen A. Gelmon, Louise Bordeleau, Haji Chalchal, Saroj Niraula, Ido Wolf, Elżbieta Senkus, François Duhoux, Randal D’hondt, Sylvie Luce, Daphné t’Kint de Roodenbeke, Konstantinos Papadimitriou, Marleen Borms, Claire Quaghebeur, William Jacot, Etienne Brain, Laurence Venat‐Bouvet, Alain Lortholary, Zbigniew Nowecki, Fátima Cardoso, Richard Hayward, Santiago Bella, Mauricio Fernández Lazzaro, N. Pilnik, Luis Fein, C. Blajman, Guillermo Lerzo, Mirta Varela, Juan José Zarbá, Diego Kaen, Maria Victoria Constanzo, Joke Tio, Wulf Siggelkow, Christian Jackisch, Eva Maria Grischke, D.-M. Zahm, Sara Tato-Varela, Sabine Schmatloch, Peter Klare, Andrea Stefek, Kerstin Rhiem, Oliver Hoffmann, Sherko Kümmel, Mustafa Deryal, Isolde Gröll, P. Ledwon, Christoph Uleer, Petra Krabisch, Jochem Potenberg, Maren Darsow, Tjoung‐Won Park‐Simon, Heinz‐Gert Höffkes, Till‐Oliver Emde, Gerd Graffunder, Oliver Tomé, Dirk Forstmeyer, Jürgen Terhaag, Christoph Salat, Karin Kast, Steffi Weniger, Carsten Schreiber, Bernhard Heinrich, Max Dieterich, Michaela Penelope Wüllner, Raquel Andrés Conejero, José Á. García-Sáenz, Lourdes Calvo Martinez, Angels Arcusa Lanza, Serafín Morales Murillo, Fernando Henao, Salvador Blanch Tormo, Isabel Álvarez López, Juan Ignacio Delgado Mingorance, Elena Álvarez Gomez, Marta Santisteban, Josefina Cruz Jurado, Vanesa Quiroga, Manuel Ruiz Borrego, Eduardo Martínez de Dueñas, Jose Enrique Alés Martínez, Juan de la Haba-Rodríguez, Noelia Martínez-Jáñez, Álvaro Rodríguez Lescure, Antonio Antón Torres, Gema Llort Crusades, Santiago González-Santiago, Antonia Marquez Aragones, Ana Laura Ortega Granados, A. Barnadas Molins, José Ignacio Chacón, M. Martín Jiménez, Ana Santaballa Bertrán, C. Rodríguez Rodríguez, Lucía González Cortijo, Elisabetta Cretella, Laura Cortesi, Enzo Maria Ruggeri, Claudio Verusio, Stefania Gori, Andrea Bonetti, Anna Maria Mosconi, Oskar T. Johannsson, Guy Jérusalem, Patrick Neven, Tünde Nagy, Graziella Pinotti, Marco Colleoni, Antônio Bernardo, Lorenzo Gianni, Eugênio Bucci, Laura Biganzoli, Konstantin J. Dedes, Urban Novak, Khalil Zaman, Jeremy Braybrooke, Matthew Winter, Daniel Rea, Muireann Kelleher, Sophie Barrett, Stephen L. Chan, Tamas Hickish, Jane Hurwitz, John Conibear, A. Jegannathen, Marina Parton, Andrew Tutt, R. Allerton, Annabel Borley, Anne Armstrong, Ellen Copson, N C Levitt, Jean Abraham, Timothy Perren, Rebecca Roylance, Kazushige Ishida, Tatsuya Toyama, Norikazu Masuda, Junichiro Watanabe, Eriko Tokunaga, Takayuki Kinoshita, Yoshiaki Rai, Masahiro Takada, Yasuhiro Yanagita, Rikiya Nakamura, Takahiro Nakayama, Yasuto Naoi, Hiroji Iwata, Seigo Nakamura, Masato Takahashi, Kenjiro Aogi, Koichiro Tsugawa, Hirofumi Mukai, Toshimi Takano, Akihiko Osaki, Nobuaki Sato, Hideko Yamauchi, Yutaka Tokuda, Mitsuya Ito, Takeki Sugimoto, Shakeela Bahadur, Patricia A. Ganz, Min J. Lu, Min J. Lu, Monica Mita, James Waisman, Jonathan A. Polikoff, Melinda L. Telli, Samantha A. Seaward, Jennifer M. Suga, Samantha A. Seaward, J. Marie Suga, Lara N. Durna, Jennifer Fu Carney, Alex R. Menter, J. Marie Suga, Ajithkumar Puthillath, Jonathan A. Polikoff, Jennifer M. Suga, Nitin Rohatgi, Jennifer M. Suga, Jonathan A. Polikoff, Jonathan A. Polikoff, James H. Feusner, Kristie Bobolis, Jonathan A. Polikoff, Peter D. Eisenberg, J. Marie Suga, Jonathan A. Polikoff, Derrick Wong, Virginia F. Borges, Alexander T. Urquhart, Erin Hofstatter, Erin W. Hofstatter, Erin W. Hofstatter, Edward C. McCarron, Claudine Isaacs, Pia Herbolsheimer, Ramya Varadarajan, Adam Raben, Ruby Anne E. Deveras, Frances Valdes-Albini, Reshma L. Mahtani, Reshma L. Mahtani, Jane Meisel, Bradley T. Sumrall, Cheryl Jones, Samuel Ofori, Kenneth N.M. Sumida, Kenneth N.M. Sumida, Mark Karwal, Deborah W. Wilbur, Singh, David Spector, John M. Schallenkamp, Douglas E. Merkel, Shelly S. Lo, Pam Khosla, Massimo Cristofanilli, Lisa Flaum, Kent Hoskins, Melody Cobleigh, Elyse A. Lambiase, Olwen Hahn, Ira A. Oliff, Bryan A. Faller, James L. Wade, Nafisa Burhani, James L. Wade, Amaryllis Gil, Harvey Einhorn, A.M. Storniolo, Brian K. Chang, Maitri Kalra, Erwin Robin, Bilal Ansari, Priyanka Sharma, Shaker R. Dakhil, Shaker R. Dakhil, Richard L. Deming, John T. Cole, John T. Cole, John T. Cole, David S. Hanson, Augusto C. Ochoa, John T. Cole, Augusto C. Ochoa, Judy E. Garber, Judy E. Garber, Harvey Zimbler, Deborah K. Armstrong, Katherine H. R. Tkaczuk, David Riseberg, Deborah K. Armstrong, Brian O’Connor, Thomas H. Openshaw, Thomas H. Openshaw, Thomas H. Openshaw, Dana Zakalik, Cynthia Vakhariya, Anne F. Schott, Michael S. Simon, Thomas J. Doyle, Tareq Al Baghdadi, Amy VanderWoude, Patrick J. Flynn, Richard T. Zera, Bret Edward Buckley Friday, Kathryn J. Ruddy, Richard T. Zera, Ron Smith, Patrick J. Flynn, Ademuyiwa, Foluso Olabisi, Robert Ellis, Jay W. Carlson, Jay W. Carlson, Marchello, Tania Benjamin, Edward A. Levine, P. Kelly Marcom, C. Harkness, Antoinette R. Tan, W. Charles, Charles Kuzma, Shonda Asaad, James E. Radford, Preston D. Steen, Madhu Unnikrishnan, Grant R. Seeger, Kirsten M.H. Leu, Mehmet S Copur, Ralph J. Hauke, Gamini S. Soori, Ralph J. Hauke, Bradley A. Arrick, Jennifer G. Reeder, Deborah Toppmeyer, Zoneddy Dayao, Sylvia Adams, Eleni Andreopoulou, Magnuson Allison, Jesus D. Anampa Mesias, Ruby Sharma, Bhuvaneswari Ramaswamy, Aaron T. Gerds, Robert R. Shenk, Howard M. Gross, Shruti Trehan, Howard M. Gross, Howard M. Gross, Howard M. Gross, Robert R. Shenk, Howard M. Gross, Robert R. Shenk, Wajeeha Razaq, Abdul Mansoor, Christie Hilton, Adam Brufsky, Chanh Huynh, Nabila Chowdhury, Susan M. Domchek, Elin R. Sigurdson, Terrence P. Cescon, Marc A. Rovito, Albert S. DeNittis, Victor G. Vogel, Thomas B. Julian, Lucy Boyle, Luis Báez-Díaz, FRANK BRESCIA, John E. Doster, Robert D. Siegel, Lucas Wong, Tejal Patel, Julie R. Nangia, Catherine A. Jones, George M. Cannon, George M. Cannon, Harry D. Bear, Hetal Vachhani, Mary Wilkinson, Marie E. Wood, Marie E. Wood, Fengting Yan, Xingwei Sui, Carol M. van Haelst, Jennifer M. Specht, Ying Zhuo, Rubina Qamar, Matthew L. Ryan, Abigail L. Stockham, Shamsuddin Virani, Rubina Qamar, Arlene A. Gayle, Rubina Qamar, Rubina Qamar, Steven J. Jubelirer, Sobha Kurian, Mohamad A. Salkeni, Niklas Loman, Barbro Linderholm, Gustav Silander, Anna‐Lotta Hallbeck, Anna von Wachenfeldt Väppling, Elsa Curtit, Catarina Cardoso, Sofía Braga, Miguel Abreu, Mafalda Casa-Nova, Mónica Nave, Eva María Ciruelos Gil, Judith Balmaña Gelpí, A. Fernandez Ortega, Josep Gumà Padró, B. Bermejo De Las Heras, María González Cao, Juan Cueva Bañuelos, Gemma Viñas Villaró, L Estevez, Jens Huober, Steffi Busch, Tanja Fehm, Antje Hahn, Andrea Gräfe, Thomas Noesselt, Thomas Dewitz, Harald Wagner, Christina Bechtner, Michael Weigel, Hans‐Christian Kolberg, Thomas Decker, Jörg Thomalla, Tobias Hesse, Nadia Harbeck, Jan Schröder Jens-Uwe Blohmer, Marc Sütterlin, Renske Altena, Chang-Fang Chiu, Shin‐Cheh Chen, Ming‐Feng Hou, Yuan‐Ching Chang, Shang‐Hung Chen, Shou-Tung Chen, Chiun‐Sheng Huang, Dah‐Cherng Yeh, Jyh-Cherng Yu, Ling‐Ming Tseng, Wei‐Pang Chung, Audrey Mailliez, Thierry Petit, Suzette Delaloge, Christelle Lévy, P. Dalivoust, Jean-Marc Extra, Marie‐Ange Mouret‐Reynier, Anne‐Claire Hardy‐Bessard, H. Simon, Tiffenn L'Haridon, Alice Mège, Sylvie Giacchetti, Camille Chakiba-Brugère, Alain Gratet, V. Pottier, Jean-­Marc Ferrero, Isabelle Tennevet, Christophe Perrin, Jean-Luc Canon, Sofie Joris, Zhimin Shao, Binghe Xu, ZeFei Jiang, Qiang Sun, Kunwei Shen, Da Pang, Jin Zhang, Shui Wang, Hongjian Yang, Ning Liao, Hong Zheng, Peifen Fu, Chuangui Song, Yongsheng Wang, Zhimin Fan, Cuizhi Geng, Olivier Trédan, László Landherr, Bella Kaufman, Rinat Yerushalmi, Beatrice Uziely, PierFranco Conte, Claudio Zamagni, Giampaolo Bianchini, Michelino De Laurentiis, Carlo Tondini, Vittorio Gebbia, Mariangela Ciccarese, Tomasz Sarosiek, Jacek Mackiewicz, Anna Słowińska, Ewa Kalinka‐Warzocha, Tomasz Huzarski, Seock‐Ah Im, Kyung Hae Jung, Joohyuk Sohn, Jee Hyun Kim, Keun Seok Lee, Yeon Hee Park, Kyoung Eun Lee, Yee Soo Chae, Eun Kyung Cho - Annals of Oncology 2022 被引用: 447

BACKGROUND: The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. PATIENTS AND METHODS: One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. RESULTS: With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. CONCLUSION: With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals.