JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T Cabazitaxel Versus Docetaxel As First-Line Therapy for Patients With Metastatic Castration-Resistant Prostate Cancer: A Randomized Phase III Trial—FIRSTANA St´ ephane Oudard, Karim Fizazi, Lisa Sengeløv, Gedske Daugaard, Fred Saad, Steinbjørn Hansen, Marie Hj¨ alm-Eriksson, Jacek Jassem, Antoine Thiery-Vuillemin, Orazio Caffo, Daniel Castellano, Paul N. Mainwaring, John Bernard, Liji Shen, Mustapha Chadjaa, and Oliver Sartor A B S T R A C T Purpose In patients with metastatic castration-resistant prostate cancer (mCRPC), overall survival (OS) is significantly improved with cabazitaxel versus mitoxantrone after prior docetaxel treatment. FIRSTANA (ClinicalTrials.gov identifier: NCT01308567) assessed whether cabazitaxel 20 mg/m 2 (C20) or 25 mg/m 2 (C25) is superior to docetaxel 75 mg/m 2 (D75) in terms of OS in patients with chemotherapy-na¨ ıve mCRPC. Patients and Methods Patients with mCRPC and Eastern Cooperative Oncology Group performance status of 0 to 2 were randomly assigned 1:1:1 to receive C20, C25, or D75 intravenously every 3 weeks plus daily prednisone. The primary end point was OS. Secondary end points included safety; progression-free survival (PFS); tumor, prostate-specific antigen, and pain response; pharmacokinetics; and health- related quality of life. Results Between May 2011 and April 2013, 1,168 patients were randomly assigned. Baseline characteristics were similar across cohorts. Median OS was 24.5 months with C20, 25.2 months with C25, and 24.3 months with D75. Hazard ratio for C20 versus D75 was 1.01 (95% CI, 0.85 to 1.20; P = .997), and hazard ratio for C25 versus D75 was 0.97 (95% CI, 0.82 to 1.16; P = .757). Median PFS was 4.4 months with C20, 5.1 months with C25, and 5.3 months with D75, with no significant dif- ferences between treatment arms. Radiographic tumor responses were numerically higher for C25 (41.6%) versus D75 (30.9%; nominal P = .037, without multiplicity test adjustment). Rates of grade 3 or 4 treatment-emergent adverse events were 41.2%, 60.1%, and 46.0% for C20, C25, and D75, respectively. Febrile neutropenia, diarrhea, and hematuria were more frequent with C25; peripheral neuropathy, peripheral edema, alopecia, and nail disorders were more frequent with D75. Conclusion C20 and C25 did not demonstrate superiority for OS versus D75 in patients with chemotherapy- na¨ ıve mCRPC. Tumor response was numerically higher with C25 versus D75; pain PFS was nu- merically improved with D75 versus C25. Cabazitaxel and docetaxel demonstrated different toxicity profiles, with overall less toxicity with C20. J Clin Oncol 35:3189-3197. © 2017 by American Society of Clinical Oncology INTRODUCTION An estimated 1.1 million men worldwide were diagnosed with prostate cancer in 2012, accounting for 15% of cancers diagnosed in men. 1 The rates are highest in Australia, New Zealand, Northern America, and Western and Northern Europe, with an estimated 307,000 deaths in 2012. 1 Most deaths are associated with development of metastatic castration-resistant prostate cancer (mCRPC). 2 A number of therapies are currently available for patients with mCRPC, including chemotherapy. 3 The current standard first-line chemotherapy for symptomatic mCRPC is docetaxel 75 mg/m 2 . 4 Recent years have seen the emergence of new therapeutic approaches for mCRPC. Androgen receptor (AR)–targeted therapies, such as abir- aterone and enzalutamide, have shown overall survival (OS) and progression-free survival (PFS) Author affiliations and support information (if applicable) appear at the end of this article. Published at jco.org on July 28, 2017. Clinical trial information: NCT01308567. Corresponding author: St ´ ephane Oudard, MD, PhD, George Pompidou European Hospital, Ren ´ e Descartes University, 20 rue Leblanc, 75908, Paris Cedex 15, France; e-mail: stephane.oudard@aphp.fr. © 2017 by American Society of Clinical Oncology 0732-183X/17/3528w-3189w/$20.00 ASSOCIATED CONTENT See accompanying Editorial on page 3175 See accompanying articles on pages 3181 and 3198 Appendix DOI: https://doi.org/10.1200/JCO. 2016.72.1068 Data Supplement DOI: https://doi.org/10.1200/JCO. 2016.72.1068 DOI: https://doi.org/10.1200/JCO.2016. 72.1068 © 2017 by American Society of Clinical Oncology 3189 VOLUME 35 • NUMBER 28 • OCTOBER 1, 2017 Downloaded from ascopubs.org by 52.73.204.196 on May 10, 2022 from 052.073.204.196 Copyright © 2022 American Society of Clinical Oncology. All rights reserved.