Efficacy and Safety of Autologous Dendritic Cell–Based Immunotherapy, Docetaxel, and Prednisone vs Placebo in Patients With Metastatic Castration-Resistant Prostate Cancer

医学恩扎鲁胺多西紫杉醇内科学前列腺癌安慰剂肿瘤科随机对照试验强的松癌症化疗病理雄激素受体替代医学

作者

Nicholas J. Vogelzang,Tomasz M. Beer,Winald R. Gerritsen,Stéphane Oudard,Paweł Wiechno,Bożena Kukiełka-Budny,Vladimír Šámal,Jaroslav Hájek,Susan Feyerabend,Vincent Khoo,Arnulf Stenzl,Tibor Csőszi,Zoran Filipovic,Frederico Gonçalves,A. A. Prokhorov,Eric Cheung,Arif Hussain,Nuno Sousa,Amit Bahl,Syed A. Hussain,Harald Fricke,Pavla Kadlecová,Tomáš Scheiner,Roman Korolkiewicz,Jiřina Bartůňková,Radek Špíšek,Walter M. Stadler,Arthur Berg,Karl‐Heinz Kurth,Celestia S. Higano,Matti Aapro,Michael Krainer,Stephan Hruby,Johannes Meran,S. Polyakov,Jean‐Pascal Machiels,Thierry Roumeguère,Koen Ackaert,Nicolaas Lumen,Thierry Gil,Velko Minchev,Antoaneta Tomova,Borislav D. Dimitrov,Marchela Koleva,Antonio Juretić,Ana Fröbe,Željko Vojnović,Martin Drabek,L Jarolı́m,Tomáš Büchler,Eva Kindlová,Jan Schraml,Milada Zemanová,Prausova Jana,Bohuslav Melichar,Martina Chodacká,Jan Jansa,Gedske Daugaard,Nicolas Delonchamps,Brigitte Duclos,Stéphane Culine,G. Deplanque,Sylvestre Le Moulec,Peter Hammerer,Gerald Rodemer,Manuel Ritter,Axel S. Merseburger,Marc‐Oliver Grimm,Ilija Damjanoski,Manfred Wirth,Martin Burmester,Kurt Miller,Jan Herden,Bastian Keck,Christian Wuelfing,Alexander Winter,Martin Boegemann,Ingo Kausch von Schmeling,Paolo Fornara,E. Jaeger,G. Bodoky,Zsuzsanna Pápai,Géza Böszörményi-Nagy,Paola Vanella,Héctor Soto Parrà,Rodolfo Passalacqua,Francesco Ferraù,Michele Maio,Lucia Fratino,Enrico Cortesi,Gunta Purkalne,Jolita Asadauskienė,Rasa Jančiauskienė,Skaistė Tulytė,Alvydas Česas,Marco B. Polée,Brigitte C.M. Haberkorn,Fons van de Eertwegh,Pieter van den Berg,Aart Beeker,Peter Nieboer,Romuald Zdrojowy,Elżbieta Starosławska,Jacek Fijuth,Bożena Sikora-Kupis,Boguslawa Karaszewska,Isabel Fernandes,Gabriela Sousa,Tânia Rodrigues,Zoran Džamić,Nada Babović,B Cvetkovic,Roman Sokol,J Mikuláš,Martin Gajdoš,Marek Brezovsky,I. Minčík,J. Breza,José Ángel Arranz,Virginia Calvo,Gabriel Rubio,M. Sánchez Chapado,Pablo Gajete Boreu,A. Montesa,David Olmos,Begoña Mellado,Daniel Castellano,Javier Puente,Erling Karlsson,Johan Ahlgren,Hardev Pandha,Danish Mazhar,Maria Vilarino-Varela,Tony Elliott,Ian Pedley,Anjali Zarkar,Amy Law,Dennis Slater,Gary Karlin,Yu‐Ning Wong,Charles H. Redfern,Rakesh Gaur,Robert McCroskey,David T. Clarkson,Manish Agrawal,Mikhail Shtivelband,Luke T. Nordquist,Nagla Fawzy Abdel Karim,Ralph J. Hauke,Thomas W. Flaig,Haresh Jhangiani,Rakesh Singal,Brian S. Choi,Evangeline Reyes,John M. Corman,Clara Hwang,Leonard J. Appleman,Edward F. McClay,Mark T. Fleming,Vijay Gunuganti,Eric Cheung,Benjamin A. Gartrell,Alton Sartor,Stephen K. Williamson,Jitendra G. Gandhi,Ian D. Schnadig,John P. Burke,Stuart H. Bloom,Neal D. Shore,Tina Mayer,William Oh,Alan H. Bryce,Laurence Belkoff,Ulka N. Vaishampayan,Sanjiv S. Agarwala,Ömer Küçük,Apurv Agrawal,William Walsh,Bernard J. Poiesz,Lauren C. Harshman,Nancy A. Dawson,Sanjay Sharma

出处

期刊：JAMA Oncology [American Medical Association]
日期：2022-02-10 卷期号：8 (4): 546-546 被引量：45

链接

nih.gov nih.govdoi.org

标识

DOI：10.1001/jamaoncol.2021.7298

摘要

Importance

DCVAC/PCa is an active cellular immunotherapy designed to initiate an immune response against prostate cancer.

Objective

To evaluate the efficacy and safety of DCVAC/PCa plus chemotherapy followed by DCVAC/PCa maintenance treatment in patients with metastatic castration-resistant prostate cancer (mCRPC).

Design, Setting, and Participants

The VIABLE double-blind, parallel-group, placebo-controlled, phase 3 randomized clinical trial enrolled patients with mCRPC among 177 hospital clinics in the US and Europe between June 2014 and November 2017. Data analyses were performed from December 2019 to July 2020.

Interventions

Eligible patients were randomized (2:1) to receive DCVAC/PCa (add-on and maintenance) or placebo, both in combination with chemotherapy (docetaxel plus prednisone). The stratification was applied according to geographical region (US or non-US), prior therapy (abiraterone, enzalutamide, or neither), and Eastern Cooperative Oncology Group performance status (0-1 or 2). DCVAC/PCa or placebo was administered subcutaneously every 3 to 4 weeks (up to 15 doses).

Main Outcomes and Measures

The primary outcome was overall survival (OS), defined as the time from randomization until death due to any cause, in all randomized patients. Survival was compared using 2-sided log-rank test stratified by geographical region, prior therapy with abiraterone and/or enzalutamide, and Eastern Cooperative Oncology Group performance status.

Results

A total of 1182 men with mCRPC (median [range] age, 68 [46-89] years) were randomized to receive DCVAC/PCa (n = 787) or placebo (n = 395). Of these, 610 (81.8%) started DCVAC/PCa, and 376 (98.4%) started placebo. There was no difference in OS between the DCVAC/PCa and placebo groups in all randomized patients (median OS, 23.9 months [95% CI, 21.6-25.3] vs 24.3 months [95% CI, 22.6-26.0]; hazard ratio, 1.04; 95% CI, 0.90-1.21;P = .60). No differences in the secondary efficacy end points (radiological progression-free survival, time to prostate-specific antigen progression, or skeletal-related events) were observed. Treatment-emergent adverse events related to DCVAC/PCa or placebo occurred in 69 of 749 (9.2%) and 48 of 379 (12.7%) patients, respectively. The most common treatment-emergent adverse events (DCVAC/PCa [n = 749] vs placebo [n = 379]) were fatigue (271 [36.2%] vs 152 [40.1%]), alopecia (222 [29.6%] vs 130 [34.3%]), and diarrhea (206 [27.5%] vs 117 [30.9%]).

Conclusions and Relevance

In this phase 3 randomized clinical trial, DCVAC/PCa combined with docetaxel plus prednisone and continued as maintenance treatment did not extend OS in patients with mCRPC and was well tolerated.

Trial Registration

ClinicalTrials.gov Identifier:NCT02111577

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