Durvalumab plus platinum–etoposide versus platinum–etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial
2019; Elsevier BV; Volume: 394; Issue: 10212 Linguagem: Inglês
10.1016/s0140-6736(19)32222-6
ISSN1474-547X
AutoresLuis Paz‐Ares, Mikhail Dvorkin, Yuanbin Chen, Niels Reinmuth, Katsuyuki Hotta, Dmytro Trukhin, Galina Statsenko, Maximilian J. Hochmair, Mustafa Özgüroğlu, Jun Ho Ji, Олександр Войтко, Artem Poltoratskiy, Santiago Ponce, Francesco Verderame, Libor Havel, Igor Bondarenko, Andrzej Każarnowicz, György Losonczy, Nikolay Conev, J. Armstrong, Natalie Byrne, Norah J. Shire, Haiyi Jiang, Jonathan W. Goldman, Emilio Batagelj, Ignacio Casarini, Anea Viviana Pastor, S. Sena, Juan José Zarbá, Otto C. Burghuber, Sylvia Hartl, Maximilian J. Hochmair, Bernd Lamprecht, Michael Studnicka, Luís Alberto Schlittler, Fabrício Augusto Martinelli de Oliveira, Aknar Calabrich, Gustavo Girotto, Peo Dos Reis, Carlos Fausto Nino Gorini, Peo Rafael Martins De Marchi, Clarissa Baldotto, Cláudia Vaz de Melo Sette, Mauro Zukin, Nikolay Conev, Assen Dudov, Rumyana Ilieva, Krassimir Koynov, Rositsa Krasteva, Ivan Tonev, Spartak Valev, Violetka Venkova, Minghong Bi, Chengshui Chen, Yuan Chen, Zhendong Chen, Jian Fang, Jifeng Feng, Zhigang Han, Jie Hu, Yi Hu, Xing Li, Zongan Liang, Lin Zhong, Rui Ma, Shenglin Ma, Kejun Nan, Yongqian Shu, Kai Wang, Mengzhao Wang, Gang Wu, Nong Yang, Zhixiong Yang, Helong Zhang, Wei Zhang, Jun Zhao, Yanqiu Zhao, Caicun Zhou, Jianying Zhou, Xiangdong Zhou, Libor Havel, Vı́tězslav Kolek, Leona Koubková, Jaromı́r Roubec, Jana Skřičková, Milada Zemanová, C. Chouaïd, Werner Hilgers, H. Léna, Denis Moro‐Sibilot, G. Robinet, Pierre-Jean Souquet, Jürgen Alt, Helge Bischoff, Christian Grohé, Eckart Laack, Susanne Lang, Jens Panse, Niels Reinmuth, Christian Schulz, Krisztina Bogos, Eszter Csánky, Anea Fülöp, Zsolt Horváth, Judit Kósa, Ibolya Laczó, György Losonczy, Gábor Pajkos, Zsuzsanna Pápai, Zsolt Pápai Székely, Veronika Sárosi, A Somfay, Éva Somogyiné Ezer, Anás Telekes, Jair Bar, Maya Gottfried, Norman Heching, Alona Zer, Roberta Bartolucci, Anna Bettini, Angelo Delmonte, Marina Chiara Garassino, Mauro Minelli, Fausto Roila, Francesco Verderame, Shinji Atagi, Koichi Azuma, Hisatsugu Goto, Kōichi Goto, Yu Hara, Hidetoshi Hayashi, Toyoaki Hida, Katsuyuki Hotta, Kenya Kanazawa, Shintaro Kanda, Young Hak Kim, Shoichi Kuyama, Tadashi Maeda, Masahiro Morise, Yasuharu Nakahara, Makoto Nishio, Naoyuki Nogami, Isamu Okamoto, Haruhiro Saito, Masahiro Shinoda, Shigeki Umemura, Tatsuya Yoshida, Niels Claessens, Robin Cornelissen, Lizza Heniks, J.T.J.N. Hiltermann, Egbert F. Smit, Agnes Staal van den Brekel, Andrzej Każarnowicz, Dariusz M. Kowalski, Sławomir Mańdziuk, Robert Mróz, Marek Z. Wojtukiewicz, Tudor‐Eliade Ciuleanu, Doina Ganea, Anei Ungureanu, Mikhail Dvorkin, Alexander Luft, В. Моисеенко, Artem Poltoratskiy, Dina Sakaeva, Alexey Smolin, Galina Statsenko, Alexander Vasilyev, Lyubov Vladimirova, Igor Anasina, Jozef Chovanec, Pavol Demo, Robert Godal, Peter Kasan, Marian Streško, M. Urda, Eun Kyung Cho, Jun Ho Ji, Joo-Hang Kim, Sang‐We Kim, Gyeong‐Won Lee, Jong-Seok Lee, Ki Hyeong Lee, Kyung Hee Lee, Yun Gyoo Lee, Amelia Insa, M. Dómine Gómez, Juan Ignacio Delgado Mingorance, D. Casado, Marta López Brea, M. Majem Tarruella, Teresa Morán Bueno, Alejano Navarro Mendivil, Luis Paz-Ares Rodríguez, Santiago Ponce Aix, M.R. García Campelo, Gee‐Chen Chang, Yen‐Hsun Chen, Chao‐Hua Chiu, Te‐Chun Hsia, Kang‐Yun Lee, Chien-Te Li, Chin‐Chou Wang, Yufeng Wei, Shang‐Yin Wu, Ahmet Alacacıoğlu, İrfan Çiçin, Ahmet Demirkazık, Mustafa Erman, Tuncay Göksel, Mustafa Özgüroğlu, Hryhoriy Adamchuk, Igor Bondarenko, Oleksii Kolesnik, Anna Kryzhanivska, Yuriv Ostapenko, Serhii Shevnia, Yaroslav Shparyk, Dmytro Trukhin, Grygorii Ursol, Олександр Войтко, Олександр Войтко, Ihor Vynnychenko, Sunil Babu, Yuanbin Chen, Anne C. Chiang, Winston Chua, Shaker R. Dakhil, Afshin Dowlati, Jonathan W. Goldman, Basir Haque, Rodney Jamil, Jeanna Knoble, Shailena Lakhanpal, Kailhong Mi, Petros Nikolinakos, Steven Powell, Helen J. Ross, Eric Schaefer, Jeffrey Schneider, Joseph E. Spahr, David R. Spigel, Joseph Stilwill, Christopher Sumey, Michael Williamson,
Tópico(s)Peptidase Inhibition and Analysis
ResumoMost patients with small-cell lung cancer (SCLC) have extensive-stage disease at presentation, and prognosis remains poor. Recently, immunotherapy has demonstrated clinical activity in extensive-stage SCLC (ES-SCLC). The CASPIAN trial assessed durvalumab, with or without tremelimumab, in combination with etoposide plus either cisplatin or carboplatin (platinum-etoposide) in treatment-naive patients with ES-SCLC.This randomised, open-label, phase 3 trial was done at 209 sites across 23 countries. Eligible patients were adults with untreated ES-SCLC, with WHO performance status 0 or 1 and measurable disease as per Response Evaluation Criteria in Solid Tumors, version 1.1. Patients were randomly assigned (in a 1:1:1 ratio) to durvalumab plus platinum-etoposide; durvalumab plus tremelimumab plus platinum-etoposide; or platinum-etoposide alone. All drugs were administered intravenously. Platinum-etoposide consisted of etoposide 80-100 mg/m2 on days 1-3 of each cycle with investigator's choice of either carboplatin area under the curve 5-6 mg/mL per min or cisplatin 75-80 mg/m2 (administered on day 1 of each cycle). Patients received up to four cycles of platinum-etoposide plus durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks in the immunotherapy groups and up to six cycles of platinum-etoposide every 3 weeks plus prophylactic cranial irradiation (investigator's discretion) in the platinum-etoposide group. The primary endpoint was overall survival in the intention-to-treat population. We report results for the durvalumab plus platinum-etoposide group versus the platinum-etoposide group from a planned interim analysis. Safety was assessed in all patients who received at least one dose of their assigned study treatment. This study is registered at ClinicalTrials.gov, NCT03043872, and is ongoing.Patients were enrolled between March 27, 2017, and May 29, 2018. 268 patients were allocated to the durvalumab plus platinum-etoposide group and 269 to the platinum-etoposide group. Durvalumab plus platinum-etoposide was associated with a significant improvement in overall survival, with a hazard ratio of 0·73 (95% CI 0·59-0·91; p=0·0047]); median overall survival was 13·0 months (95% CI 11·5-14·8) in the durvalumab plus platinum-etoposide group versus 10·3 months (9·3-11·2) in the platinum-etoposide group, with 34% (26·9-41·0) versus 25% (18·4-31·6) of patients alive at 18 months. Any-cause adverse events of grade 3 or 4 occurred in 163 (62%) of 265 treated patients in the durvalumab plus platinum-etoposide group and 166 (62%) of 266 in the platinum-etoposide group; adverse events leading to death occurred in 13 (5%) and 15 (6%) patients.First-line durvalumab plus platinum-etoposide significantly improved overall survival in patients with ES-SCLC versus a clinically relevant control group. Safety findings were consistent with the known safety profiles of all drugs received.AstraZeneca.
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