Stéphane Oudard, Georges Pompidou European Hospital, Rene Descartes University; Mustapha Chadjaa; Sanofi, Paris; Karim Fizazi, Institut Gustave Roussy, University of Paris Sud, Villejuif; Antoine Thiery-Vuillemin, Centre Hospitalier Universitaire Minjoz Besançon, Besançon, France; Lisa Sengeløv, Herlev Hospital, Herlev; Gedske Daugaard, Copenhagen University Hospital, Rigshospitalet, Copenhagen; Steinbjørn Hansen, Odense University Hospital, Odense, Denmark; Fred Saad, Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada; Marie Hjälm-Eriksson, Karolinska University Hospital, Stockholm, Sweden; Jacek Jassem, Medical University of Gdansk, Gdansk, Poland; Orazio Caffo, Santa Chiara Hospital, Trento, Italy; Daniel Castellano, University Hospital 12 de Octubre, Madrid, Spain; Paul N. Mainwaring, Icon Cancer Care, Brisbane, Queensland, Australia; John Bernard, Sanofi, Cambridge, MA; Liji Shen, Sanofi, Bridgewater, NJ; and Oliver Sartor, Tulane Cancer Center, New Orleans, LA.
J Clin Oncol. 2017 Oct 1;35(28):3189-3197. doi: 10.1200/JCO.2016.72.1068. Epub 2017 Jul 28.
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 (C20) or 25 mg/m (C25) is superior to docetaxel 75 mg/m (D75) in terms of OS in patients with chemotherapy-naïve 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 differences 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-naïve mCRPC. Tumor response was numerically higher with C25 versus D75; pain PFS was numerically improved with D75 versus C25. Cabazitaxel and docetaxel demonstrated different toxicity profiles, with overall less toxicity with C20.
在先前接受多西他赛治疗的转移性去势抵抗性前列腺癌（mCRPC）患者中，与米托蒽醌相比，卡巴他赛可显著改善总生存期（OS）。FIRSTANA（ClinicalTrials.gov 标识符：NCT01308567）评估了在化疗初治 mCRPC 患者中，卡巴他赛 20mg/m（C20）或 25mg/m（C25）是否优于多西他赛 75mg/m（D75）。
mCRPC 患者且东部肿瘤协作组体能状态为 0-2 分，按 1:1:1 比例随机分配接受 C20、C25 或 D75 静脉滴注，每 3 周一次，同时每日给予泼尼松。主要终点为 OS。次要终点包括安全性、无进展生存期（PFS）、肿瘤、前列腺特异性抗原和疼痛反应、药代动力学和健康相关生活质量。
2011 年 5 月至 2013 年 4 月期间，共随机分配了 1168 例患者。各组间基线特征相似。C20 组、C25 组和 D75 组的中位 OS 分别为 24.5 个月、25.2 个月和 24.3 个月。C20 与 D75 的危险比为 1.01（95%CI，0.85-1.20；P=0.997），C25 与 D75 的危险比为 0.97（95%CI，0.82-1.16；P=0.757）。C20 组、C25 组和 D75 组的中位 PFS 分别为 4.4 个月、5.1 个月和 5.3 个月，各组间无显著差异。C25 组（41.6%）较 D75 组（30.9%）的放射学肿瘤反应更高（名义 P=0.037，未调整多重性检验）。C20、C25 和 D75 组的 3/4 级治疗相关不良事件发生率分别为 41.2%、60.1%和 46.0%。C25 组更常见发热性中性粒细胞减少症、腹泻和血尿，D75 组更常见周围神经病、外周水肿、脱发和指甲疾病。
在化疗初治 mCRPC 患者中，C20 和 C25 与 D75 相比，OS 无优势。与 D75 相比，C25 组的肿瘤反应更高；与 C25 相比，D75 组的疼痛 PFS 更高。卡巴他赛和多西他赛的毒性谱不同，C20 的总体毒性更小。
