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Lancet. 2019 Nov 23;394(10212):1929-1939. doi: 10.1016/S0140-6736(19)32222-6. Epub 2019 Oct 4.

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.

Collaborators (222)

Batagelj E, Casarini I, Pastor AV, Sena SN, Zarba JJ, Burghuber O, Hartl S, Hochmair MJ, Lamprecht B, Studnicka M, Alberto Schlittler L, Augusto Martinelli de Oliveira F, Calabrich A, Colagiovanni Girotto G, Dos Reis P, Fausto Nino Gorini C, Rafael Martins De Marchi P, Serodio da Rocha Baldotto C, Sette C, Zukin M, Conev NV, Dudov A, Ilieva R, Koynov K, Krasteva R, Tonev I, Valev S, Venkova V, Bi M, Chen C, Chen Y, Chen Z, Fang J, Feng J, Han Z, Hu J, Hu Y, Li W, Liang Z, Lin Z, Ma R, Ma S, Nan K, Shu Y, Wang K, Wang M, Wu G, Yang N, Yang Z, Zhang H, Zhang W, Zhao J, Zhao Y, Zhou C, Zhou J, Zhou X, Havel L, Kolek V, Koubkova L, Roubec J, Skrickova J, Zemanova M, Chouaid C, Hilgers W, Lena H, Moro-Sibilot D, Robinet G, Souquet PJ, Alt J, Bischoff H, Grohe C, Laack E, Lang S, Panse J, Reinmuth N, Schulz C, Bogos K, Csánky E, Fülöp A, Horváth Z, Kósa J, Laczó I, Losonczy G, Pajkos G, Pápai Z, Pápai Székely Z, Sárosi V, Somfay A, Somogyiné Ezer É, Telekes A, Bar J, Gottfried M, Heching NI, Zer Kuch A, Bartolucci R, Bettini AC, Delmonte A, Garassino MC, Minelli M, Roila F, Verderame F, Atagi S, Azuma K, Goto H, Goto K, Hara Y, Hayashi H, Hida T, Hotta K, Kanazawa K, Kanda S, Kim YH, Kuyama S, Maeda T, Morise M, Nakahara Y, Nishio M, Nogami N, Okamoto I, Saito H, Shinoda M, Umemura S, Yoshida T, Claessens N, Cornelissen R, Heniks L, Hiltermann J, Smit E, Staal van den Brekel A, Kazarnowicz A, Kowalski D, Mańdziuk S, Mróz R, Wojtukiewicz M, Ciuleanu T, Ganea D, Ungureanu A, Dvorkin M, Luft A, Moiseenko V, Poltoratskiy A, Sakaeva D, Smolin A, Statsenko G, Vasilyev A, Vladimirova L, Anasina I, Chovanec J, Demo P, Godal R, Kasan P, Stresko M, Urda M, Cho EK, Ji JH, Kim JH, Kim SW, Lee GW, Lee JS, Lee KH, Lee KH, Lee YG, Amelia Insa Molla M, Domine Gomez M, Ignacio Delgado Mingorance J, Isla Casado D, Lopez Brea M, Majem Tarruella M, Morán Bueno T, Navarro Mendivil A, Paz-Ares Rodríguez L, Ponce Aix S, Rosario Garcia Campelo M, Chang GC, Chen YH, Chiu CH, Hsia TC, Lee KY, Li CT, Wang CC, Wei YF, Wu SY, Alacacıoğlu A, Çiçin I, Demirkazik A, Erman M, Göksel T, Özgüroğlu M, Adamchuk H, Bondarenko I, Kolesnik O, Kryzhanivska A, Ostapenko Y, Shevnia S, Shparyk Y, Trukhin D, Ursol G, Voitko N, Voitko O, Vynnychenko I, Babu S, Chen Y, Chiang A, Chua W, Dakhil S, Dowlati A, Goldman JW, Haque B, Jamil R, Knoble J, Lakhanpal S, Mi K, Nikolinakos P, Powell S, Ross H, Schaefer E, Schneider J, Spahr J, Spigel D, Stilwill J, Sumey C, Williamson M.

Author information

1
Department of Medical Oncology, Hospital Universitario 12 de Octubre, H120-CNIO Lung Cancer Unit, Universidad Complutense and Ciberonc, Madrid, Spain. Electronic address: lpazaresr@seom.org.
2
BHI of Omsk Region Clinical Oncology Dispensary, Omsk, Russia.
3
Cancer and Hematology Centers of Western Michigan, Grand Rapids, MI, USA.
4
Asklepios Lung Clinic, Munich-Gauting, Germany.
5
Okayama University Hospital, Okayama, Japan.
6
Odessa National Medical University, Odessa, Ukraine.
7
Omsk Regional Cancer Center, Omsk, Russia.
8
Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Krankenhaus Nord, Vienna, Austria.
9
Istanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul, Turkey.
10
Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea.
11
Kyiv City Clinical Oncological Centre, Kiev, Ukraine.
12
Petrov Research Institute of Oncology, St Petersburg, Russia.
13
Department of Medical Oncology, Hospital Universitario 12 de Octubre, H120-CNIO Lung Cancer Unit, Universidad Complutense and Ciberonc, Madrid, Spain.
14
AO Ospedali Riuniti PO Vincenzo Cervello, Palermo, Italy.
15
Thomayer Hospital, First Faculty of Medicine, Charles University, Prague, Czechia.
16
Dnipropetrovsk Medical Academy, Dnipro, Ukraine.
17
Tuberculosis and Lung Disease Hospital, Olsztyn, Poland.
18
Semmelweis University, Budapest, Hungary.
19
Clinic of Medical Oncology, UMHAT St Marina, Varna, Bulgaria.
20
AstraZeneca, Cambridge, UK.
21
AstraZeneca, Gaithersburg, MD, USA.
22
David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

Abstract

BACKGROUND:

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.

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/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.

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.

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