Durvalumab, with or without tremelimumab, plus platinum–etoposide versus platinum–etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial

Goldman, J.W.; Dvorkin, M.; Chen, Y.; Reinmuth, N.; Hotta, K.; Trukhin, D.; Statsenko, G.; Hochmair, M.J.; Özgüroğlu, M.; Ji, J.H.; Garassino, M.C.; Voitko, O.; Poltoratskiy, A.; Ponce, S.; Verderame, F.; Havel, L.; Bondarenko, I.; Każarnowicz, A.; Losonczy, G.; Conev, N.V.; Armstrong, J.; Byrne, N.; Thiyagarajah, P.; Jiang, H.; Paz-Ares, L.; Trukhin, D.; Voitko, N.; Poltoratskiy, A.; Chen, Y.; Kazarnowicz, A.; Paz-Ares, L.; Özgüroglu, M.; Conev, N.; Hochmair, M.; Burghuber, O.; Havel, L.; Çiçin, I.; Losonczy, G.; Moiseenko, V.; Erman, M.; Kowalski, D.; Wojtukiewicz, M.; Adamchuk, H.; Vasilyev, A.; Shevnia, S.; Valev, S.; Reinmuth, N.; Ji, J.H.; Insa Molla, M.A.; Ursol, G.; Chiang, A.; Hartl, S.; Horváth, Z.; Pajkos, G.; Verderame, F.; Hotta, K.; Kim, S.; Smolin, A.; Göksel, T.; Dakhil, S.; Roubec, J.; Bogos, K.; Garassino, M.C.; Cornelissen, R.; Lee, J.; Garcia Campelo, M.R.; Lopez, B.M.; Alacacioglu, A.; Casarini, I.; Ilieva, R.; Tonev, I.; Somfay, A.; Bar, J.; Zer, K.A.; Minelli, M.; Bartolucci, R.; Roila, F.; Saito, H.; Azuma, K.; Lee, G.; Luft, A.; Urda, M.; Delgado Mingorance, J.I.; Majem, T.M.; Spigel, D.; Koynov, K.; Zemanova, M.; Panse, J.; Schulz, C.; Pápai, S.Z.; Sárosi, V.; Delmonte, A.; Bettini, A.C.; Nishio, M.; Okamoto, I.; Hendriks, L.; Mandziuk, S.; Lee, Y.G.; Vladimirova, L.; Isla, C.D.; Domine, G.M.; Navarro, M.A.; Morán, B.T.; Wu, S.; Knoble, J.; Skrickova, J.; Venkova, V.; Hilgers, W.; Laack, E.; Bischoff, H.; Fülöp, A.; Laczó, I.; Kósa, J.; Telekes, A.; Yoshida, T.; Kanda, S.; Hida, T.; Hayashi, H.; Maeda, T.; Kawamura, T.; Nakahara, Y.; Claessens, N.; Lee, K.H.; Chiu, C.; Lin, S.; Li Chien-Te; Demirkazik, A.; Schaefer, E.; Nikolinakos, P.; Schneider, J.; Babu, S.; Lamprecht, B.; Studnicka, M.; Fausto Nino, G.C.; Kultan, J.; Kolek, V.; Souquet, P.; Moro-Sibilot, D.; Gottfried, M.; Smit, E.; Lee, K.H.; Kasan, P.; Chovanec, J.; Goloborodko, O.; Kolesnik, O.; Ostapenko, Y.; Lakhanpal, S.; Haque, B.; Chua, W.; Stilwill, J.; Sena, S.N.; Girotto, G.C.; De Marchi Pedro, R.M.; Martinelli de Oliveira, F.A.; Dos Reis, P.; Krasteva, R.; Zhao, Y.; Chen, C.; Koubkova, L.; Robinet, G.; Chouaid, C.; Grohe, C.; Alt, J.; Csánky, E.; Somogyiné, E.É.; Heching, N.I.; Kim, Y.H.; Aatagi, S.; Kuyama, S.; Harada, D.; Nogami, N.; Nokihara, H.; Goto, H.; Staal van den, B.A.; Cho, E.K.; Kim, J.; Ganea, D.; Ciuleanu, T.; Popova, E.; Sakaeva, D.; Stresko, M.; Demo, P.; Godal, R.; Wei, Y.; Chen, Y.; Hsia, T.; Lee, K.; Chang, H.; Wang, C.; Dowlati, A.; Sumey, C.; Powell, S.; Goldman, J.; Zarba, J.J.; Batagelj, E.; Pastor, A.V.; Zukin, M.; Baldotto Clarissa, S.d.; Schlittler, L.A.; Calabrich, A.; Sette, C.; Dudov, A.; Zhou, C.; Lena, H.; Lang, S.; Pápai, Z.; Goto, K.; Umemura, S.; Kanazawa, K.; Hara, Y.; Shinoda, M.; Morise, M.; Hiltermann, J.; Mróz, R.; Ungureanu, A.; Andrasina, I.; Chang, G.; Vynnychenko, I.; Shparyk, Y.; Kryzhanivska, A.; Ross, H.; Mi, K.; Jamil, R.; Williamson, M.; Spahr, J.; Han, Z.; Wang, M.; Yang, Z.; Hu, J.; Li Wei; Zhao, J.; Feng, J.; Ma, S.; Zhou, X.; Liang, Z.; Hu, Y.; Chen, Y.; Bi, M.; Shu, Y.; Nan, K.; Zhou, J.; Zhang, W.; Ma, R.; Yang, N.; Lin, Z.; Wu, G.; Fang, J.; Zhang, H.; Wang, K.; Chen, Z.

Авторы: Goldman Jonathan W., Dvorkin Mikhail, Chen Yuanbin, Reinmuth Niels, Hotta Katsuyuki, Trukhin Dmytro, Statsenko Galina, Hochmair Maximilian J., Özgüroğlu Mustafa, Ji Jun Ho, Garassino Marina Chiara, Voitko Oleksandr, Poltoratskiy Artem, Ponce Santiago, Verderame Francesco, Havel Libor, Bondarenko Igor, Każarnowicz Andrzej, Losonczy György, Conev Nikolay V., Armstrong Jon, Byrne Natalie, Thiyagarajah Piruntha, Jiang Haiyi, Paz-Ares Luis, Trukhin Dmytro, Voitko Nataliia, Poltoratskiy Artem, Chen Yuanbin, Kazarnowicz Andrzej, Paz-Ares Luis, Özgüroglu Mustafa, Conev Nikolay, Hochmair Maximilian, Burghuber Otto, Havel Libor, Çiçin Irfan, Losonczy György, Moiseenko Vladimir, Erman Mustafa, Kowalski Dariusz, Wojtukiewicz Marek, Adamchuk Hryhoriy, Vasilyev Alexander, Shevnia Serhii, Valev Spartak, Reinmuth Niels, Ji Jun Ho, Insa Molla Maria Amelia, Ursol Grygorii, Chiang Anne, Hartl Sylvia, Horváth Zsolt, Pajkos Gábor, Verderame Francesco, Hotta Katsuyuki, Kim Sang-We, Smolin Alexey, Göksel Tuncay, Dakhil Shaker, Roubec Jaromir, Bogos Krisztina, Garassino Marina Chiara, Cornelissen Robin, Lee Jong-Seok, Garcia Campelo Maria Rosario, Lopez Brea Marta, Alacacioglu Ahmet, Casarini Ignacio, Ilieva Rumyana, Tonev Ivan, Somfay Attila, Bar Jair, Zer Kuch Alona, Minelli Mauro, Bartolucci Roberta, Roila Fausto, Saito Haruhiro, Azuma Koichi, Lee Gyeong-Won, Luft Alexander, Urda Michal, Delgado Mingorance Juan Ignacio, Majem Tarruella Margarita, Spigel David, Koynov Krassimir, Zemanova Milada, Panse Jens, Schulz Christian, Pápai Székely Zsolt, Sárosi Veronika, Delmonte Angelo, Bettini Anna Cecilia, Nishio Makoto, Okamoto Isamu, Hendriks Lizza, Mandziuk Slawomir, Lee Yun Gyoo, Vladimirova Lyubov, Isla Casado Dolores, Domine Gomez Manuel, Navarro Mendivil Alejandro, Morán Bueno Teresa, Wu Shang-Yin, Knoble Jeanna, Skrickova Jana, Venkova Violetka, Hilgers Werner, Laack Eckart, Bischoff Helge, Fülöp Andrea, Laczó Ibolya, Kósa Judit, Telekes András, Yoshida Tatsuya, Kanda Shintaro, Hida Toyoaki, Hayashi Hidetoshi, Maeda Tadashi, Kawamura Tetsuji, Nakahara Yasuharu, Claessens Niels, Lee Ki Hyeong, Chiu Chao-Hua, Lin Sheng-Hao, Li Chien-Te, Demirkazik Ahmet, Schaefer Eric, Nikolinakos Petros, Schneider Jeffrey, Babu Sunil, Lamprecht Bernd, Studnicka Michael, Fausto Nino Gorini Carlos, Kultan Juraj, Kolek Vitezslav, Souquet Pierre-Jean, Moro-Sibilot Denis, Gottfried Maya, Smit Egbert, Lee Kyung Hee, Kasan Peter, Chovanec Jozef, Goloborodko Olexandr, Kolesnik Oleksii, Ostapenko Yuriy, Lakhanpal Shailendra, Haque Basir, Chua Winston, Stilwill Joseph, Sena Susana Noemi, Girotto Gustavo Colagiovanni, De Marchi Pedro Rafael Martins, Martinelli de Oliveira Fabricio Augusto, Dos Reis Pedro, Krasteva Rositsa, Zhao Yanqiu, Chen Chengshui, Koubkova Leona, Robinet Gilles, Chouaid Christos, Grohe Christian, Alt Jürgen, Csánky Eszter, Somogyiné Ezer Éva, Heching Norman Isaac, Kim Young Hak, Aatagi Shinji, Kuyama Shoichi, Harada Daijiro, Nogami Naoyuki, Nokihara Hiroshi, Goto Hisatsugu, Staal van den Brekel Agnes, Cho Eun Kyung, Kim Joo-Hang, Ganea Doina, Ciuleanu Tudor, Popova Ekaterina, Sakaeva Dina, Stresko Marian, Demo Pavol, Godal Robert, Wei Yu-Feng, Chen Yen-Hsun, Hsia Te-Chun, Lee Kang-Yun, Chang Huang-Chih, Wang Chin-Chou, Dowlati Afshin, Sumey Christopher, Powell Steven, Goldman Jonathan, Zarba Juan Jose, Batagelj Emilio, Pastor Andrea Viviana, Zukin Mauro, Baldotto Clarissa Serodio da Rocha, Schlittler Luis Alberto, Calabrich Aknar, Sette Claudia, Dudov Asen, Zhou Caicun, Lena Hervé, Lang Susanne, Pápai Zsuzsanna, Goto Koichi, Umemura Shigeki, Kanazawa Kenya, Hara Yu, Shinoda Masahiro, Morise Masahiro, Hiltermann Jeroen, Mróz Robert, Ungureanu Andrei, Andrasina Igor, Chang Gee-Chen, Vynnychenko Ihor, Shparyk Yaroslav, Kryzhanivska Anna, Ross Helen, Mi Kailhong, Jamil Rodney, Williamson Michael, Spahr Joseph, Han Zhigang, Wang Mengzhao, Yang Zhixiong, Hu Jie, Li Wei, Zhao Jun, Feng Jifeng, Ma Shenglin, Zhou Xiangdong, Liang Zongan, Hu Yi, Chen Yuan, Bi Minghong, Shu Yongqian, Nan Kejun, Zhou Jianying, Zhang Wei, Ma Rui, Yang Nong, Lin Zhong, Wu Gang, Fang Jian, Zhang Helong, Wang Kai, Chen Zhendong
Журнал: Lancet Oncology
Том: 22
Номер: 1
Год издания: 2021
Издательство: The Lancet Publishing Group
Местоположение издательства: United Kingdom
Первая страница: 51
Последняя страница: 65
DOI: 10.1016/s1470-2045(20)30539-8
Аннотация: Background: First-line durvalumab plus etoposide with either cisplatin or carboplatin (platinum-etoposide) showed a significant improvement in overall survival versus platinum-etoposide alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) in the CASPIAN study. Here we report updated results, including the primary analysis for overall survival with durvalumab plus tremelimumab plus platinum-etoposide versus platinum-etoposide alone. Methods: CASPIAN is an ongoing, open-label, sponsor-blind, randomised, controlled phase 3 trial at 209 cancer treatment centres in 23 countries worldwide. Eligible patients were aged 18 years or older (20 years in Japan) and had treatment-naive, histologically or cytologically documented ES-SCLC, with a WHO performance status of 0 or 1. Patients were randomly assigned (1:1:1) in blocks of six, stratified by planned platinum, using an interactive voice-response or web-response system to receive intravenous durvalumab plus tremelimumab plus platinum-etoposide, durvalumab plus platinum-etoposide, or platinum-etoposide alone. In all groups, patients received 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/min or cisplatin 75-80 mg/m2 on day 1 of each cycle. Patients in the platinum-etoposide group received up to six cycles of platinum-etoposide every 3 weeks and optional prophylactic cranial irradiation (investigator's discretion). Patients in the immunotherapy groups received 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. The two primary endpoints were overall survival for durvalumab plus platinum-etoposide versus platinum-etoposide and for durvalumab plus tremelimumab plus platinum-etoposide versus platinum-etoposide in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered at ClinicalTrials.gov, NCT03043872. Findings: Between March 27, 2017, and May 29, 2018, 972 patients were screened and 805 were randomly assigned (268 to durvalumab plus tremelimumab plus platinum-etoposide, 268 to durvalumab plus platinum-etoposide, and 269 to platinum-etoposide). As of Jan 27, 2020, the median follow-up was 25·1 months (IQR 22·3-27·9). Durvalumab plus tremelimumab plus platinum-etoposide was not associated with a significant improvement in overall survival versus platinum-etoposide (hazard ratio [HR] 0·82 [95% CI 0·68-1·00]; p=0·045); median overall survival was 10·4 months (95% CI 9·6-12·0) versus 10·5 months (9·3-11·2). Durvalumab plus platinum-etoposide showed sustained improvement in overall survival versus platinum-etoposide (HR 0·75 [95% CI 0·62-0·91]; nominal p=0·0032); median overall survival was 12·9 months (95% CI 11·3-14·7) versus 10·5 months (9·3-11·2). The most common any-cause grade 3 or worse adverse events were neutropenia (85 [32%] of 266 patients in the durvalumab plus tremelimumab plus platinum-etoposide group, 64 [24%] of 265 patients in the durvalumab plus platinum-etoposide group, and 88 [33%] of 266 patients in the platinum-etoposide group) and anaemia (34 [13%], 24 [9%], and 48 [18%]). Any-cause serious adverse events were reported in 121 (45%) patients in the durvalumab plus tremelimumab plus platinum-etoposide group, 85 (32%) in the durvalumab plus platinum-etoposide group, and 97 (36%) in the platinum-etoposide group. Treatment-related deaths occurred in 12 (5%) patients in the durvalumab plus tremelimumab plus platinum-etoposide group (death, febrile neutropenia, and pulmonary embolism [n=2 each]; enterocolitis, general physical health deterioration and multiple organ dysfunction syndrome, pneumonia, pneumonitis and hepatitis, respiratory failure, and sudden death [n=1 each]), six (2%) patients in the durvalumab plus platinum-etoposide group (cardiac arrest, dehydration, hepatotoxicity, interstitial lung disease, pancytopenia, and sepsis [n=1 each]), and two (1%) in the platinum-etoposide group (pancytopenia and thrombocytopenia [n=1 each]). Interpretation: First-line durvalumab plus platinum-etoposide showed sustained overall survival improvement versus platinum-etoposide but the addition of tremelimumab to durvalumab plus platinum-etoposide did not significantly improve outcomes versus platinum-etoposide. These results support the use of durvalumab plus platinum-etoposide as a new standard of care for the first-line treatment of ES-SCLC.
Добавил в систему: Владимирова Любовь Юрьевна

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Durvalumab, with or without tremelimumab, plus platinum–etoposide versus platinum–etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trialстатья