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.

Aged Antibodies, Monoclonal / administration & dosage Antibodies, Monoclonal, Humanized / administration & dosage Antineoplastic Agents, Immunological / administration & dosage Antineoplastic Agents, Phytogenic / administration & dosage Antineoplastic Combined Chemotherapy Protocols Carboplatin / administration & dosage Cisplatin / administration & dosage Drug Administration Schedule Etoposide / administration & dosage Female Humans Lung Neoplasms / drug therapy Male Middle Aged Progression-Free Survival Small Cell Lung Carcinoma / drug therapy

Journal

Lancet (London, England)

ISSN: 1474-547X

Titre abrégé: Lancet

Pays: England

ID NLM: 2985213R

Informations de publication

Date de publication:
23 11 2019

Historique:

received: 21 08 2019

revised: 16 09 2019

accepted: 16 09 2019

pubmed: 9 10 2019

medline: 18 12 2019

entrez: 9 10 2019

Statut: ppublish

Résumé

Most 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/m 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.

Sections du résumé

BACKGROUND

METHODS

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/m

FINDINGS

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.

INTERPRETATION

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.

FUNDING

AstraZeneca.

Identifiants

DOI: 10.1016/S0140-6736(19)32222-6 PMID: 31590988

pubmed: 31590988

pii: S0140-6736(19)32222-6

doi: 10.1016/S0140-6736(19)32222-6

pii:

doi:

Substances chimiques

Antibodies, Monoclonal 0

Antibodies, Monoclonal, Humanized 0

Antineoplastic Agents, Immunological 0

Antineoplastic Agents, Phytogenic 0

durvalumab 28X28X9OKV

Etoposide 6PLQ3CP4P3

Carboplatin BG3F62OND5

Cisplatin Q20Q21Q62J

tremelimumab QEN1X95CIX

Banques de données

ClinicalTrials.gov

['NCT03043872']

Types de publication

Clinical Trial, Phase III Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

1929-1939

Investigateurs

Emilio Batagelj (E)

Ignacio Casarini (I)

Anea Viviana Pastor (AV)

Susana Noemi Sena (SN)

Juan Jose Zarba (JJ)

Otto Burghuber (O)

Sylvia Hartl (S)

Maximilian J Hochmair (MJ)

Bernd Lamprecht (B)

Michael Studnicka (M)

Luis Alberto Schlittler (L)

Fabricio Augusto Martinelli de Oliveira (F)

Aknar Calabrich (A)

Gustavo Colagiovanni Girotto (G)

Peo Dos Reis (P)

Carlos Fausto Nino Gorini (C)

Peo Rafael Martins De Marchi (P)

Clarissa Serodio da Rocha Baldotto (C)

Claudia Sette (C)

Mauro Zukin (M)

Nikolay V Conev (NV)

Assen Dudov (A)

Rumyana Ilieva (R)

Krassimir Koynov (K)

Rositsa Krasteva (R)

Ivan Tonev (I)

Spartak Valev (S)

Violetka Venkova (V)

Minghong Bi (M)

Chengshui Chen (C)

Yuan Chen (Y)

Zhendong Chen (Z)

Jian Fang (J)

Jifeng Feng (J)

Zhigang Han (Z)

Jie Hu (J)

Yi Hu (Y)

Wei Li (W)

Zongan Liang (Z)

Zhong Lin (Z)

Rui Ma (R)

Shenglin Ma (S)

Kejun Nan (K)

Yongqian Shu (Y)

Kai Wang (K)

Mengzhao Wang (M)

Gang Wu (G)

Nong Yang (N)

Zhixiong Yang (Z)

Helong Zhang (H)

Wei Zhang (W)

Jun Zhao (J)

Yanqiu Zhao (Y)

Caicun Zhou (C)

Jianying Zhou (J)

Xiangdong Zhou (X)

Libor Havel (L)

Vitezslav Kolek (V)

Leona Koubkova (L)

Jaromir Roubec (J)

Jana Skrickova (J)

Milada Zemanova (M)

Christos Chouaid (C)

Werner Hilgers (W)

Hervé Lena (H)

Denis Moro-Sibilot (D)

Gilles Robinet (G)

Pierre-Jean Souquet (PJ)

Jürgen Alt (J)

Helge Bischoff (H)

Christian Grohe (C)

Eckart Laack (E)

Susanne Lang (S)

Jens Panse (J)

Niels Reinmuth (N)

Christian Schulz (C)

Krisztina Bogos (K)

Eszter Csánky (E)

Anea Fülöp (A)

Zsolt Horváth (Z)

Judit Kósa (J)

Ibolya Laczó (I)

György Losonczy (G)

Gábor Pajkos (G)

Zsuzsanna Pápai (Z)

Zsolt Pápai Székely (Z)

Veronika Sárosi (V)

Attila Somfay (A)

Éva Somogyiné Ezer (É)

Anás Telekes (A)

Jair Bar (J)

Maya Gottfried (M)

Norman Isaac Heching (NI)

Alona Zer Kuch (A)

Roberta Bartolucci (R)

Anna Cecilia Bettini (AC)

Angelo Delmonte (A)

Marina Chiara Garassino (MC)

Mauro Minelli (M)

Fausto Roila (F)

Francesco Verderame (F)

Shinji Atagi (S)

Koichi Azuma (K)

Hisatsugu Goto (H)

Koichi Goto (K)

Yu Hara (Y)

Hidetoshi Hayashi (H)

Toyoaki Hida (T)

Katsuyuki Hotta (K)

Kenya Kanazawa (K)

Shintaro Kanda (S)

Young Hak Kim (YH)

Shoichi Kuyama (S)

Tadashi Maeda (T)

Masahiro Morise (M)

Yasuharu Nakahara (Y)

Makoto Nishio (M)

Naoyuki Nogami (N)

Isamu Okamoto (I)

Haruhiro Saito (H)

Masahiro Shinoda (M)

Shigeki Umemura (S)

Tatsuya Yoshida (T)

Niels Claessens (N)

Robin Cornelissen (R)

Lizza Heniks (L)

Jeroen Hiltermann (J)

Egbert Smit (E)

Agnes Staal van den Brekel (A)

Andrzej Kazarnowicz (A)

Dariusz Kowalski (D)

Slawomir Mańdziuk (S)

Robert Mróz (R)

Marek Wojtukiewicz (M)

Tudor Ciuleanu (T)

Doina Ganea (D)

Anei Ungureanu (A)

Mikhail Dvorkin (M)

Alexander Luft (A)

Vladimir Moiseenko (V)

Artem Poltoratskiy (A)

Dina Sakaeva (D)

Alexey Smolin (A)

Galina Statsenko (G)

Alexander Vasilyev (A)

Lyubov Vladimirova (L)

Igor Anasina (I)

Jozef Chovanec (J)

Pavol Demo (P)

Robert Godal (R)

Peter Kasan (P)

Marian Stresko (M)

Michal Urda (M)

Eun Kyung Cho (EK)

Jun Ho Ji (JH)

Joo-Hang Kim (JH)

Sang-We Kim (SW)

Gyeong-Won Lee (GW)

Jong-Seok Lee (JS)

Ki Hyeong Lee (KH)

Kyung Hee Lee (KH)

Yun Gyoo Lee (YG)

Maria Amelia Insa Molla (M)

Manuel Domine Gomez (M)

Juan Ignacio Delgado Mingorance (J)

Dolores Isla Casado (D)

Marta Lopez Brea (M)

Margarita Majem Tarruella (M)

Teresa Morán Bueno (T)

Alejano Navarro Mendivil (A)

Luis Paz-Ares Rodríguez (L)

Santiago Ponce Aix (S)

Maria Rosario Garcia Campelo (M)

Gee-Chen Chang (GC)

Yen-Hsun Chen (YH)

Chao-Hua Chiu (CH)

Te-Chun Hsia (TC)

Kang-Yun Lee (KY)

Chien-Te Li (CT)

Chin-Chou Wang (CC)

Yu-Feng Wei (YF)

Shang-Yin Wu (SY)

Ahmet Alacacıoğlu (A)

Irfan Çiçin (I)

Ahmet Demirkazik (A)

Mustafa Erman (M)

Tuncay Göksel (T)

Mustafa Özgüroğlu (M)

Hryhoriy Adamchuk (H)

Igor Bondarenko (I)

Oleksii Kolesnik (O)

Anna Kryzhanivska (A)

Yuriv Ostapenko (Y)

Serhii Shevnia (S)

Yaroslav Shparyk (Y)

Dmytro Trukhin (D)

Grygorii Ursol (G)

Nataliia Voitko (N)

Oleksandr Voitko (O)

Ihor Vynnychenko (I)

Sunil Babu (S)

Yuanbin Chen (Y)

Anne Chiang (A)

Winston Chua (W)

Shaker Dakhil (S)

Afshin Dowlati (A)

Jonathan W Goldman (JW)

Basir Haque (B)

Rodney Jamil (R)

Jeanna Knoble (J)

Shailena Lakhanpal (S)

Kailhong Mi (K)

Petros Nikolinakos (P)

Steven Powell (S)

Helen Ross (H)

Eric Schaefer (E)

Jeffrey Schneider (J)

Joseph Spahr (J)

David Spigel (D)

Joseph Stilwill (J)

Christopher Sumey (C)

Michael Williamson (M)

Commentaires et corrections

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