Mario Eisenberger, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Anne-Claire Hardy-Bessard, Centre Armoricain d'Oncologie, Centre Armoricain de Radiothérapie, d'Imagerie Médicale et d'Oncologie-Hôpital Privé Des Côtes d'Armor, Plérin; Loïc Mourey, Institut Claudius Regaud, l'Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse; Mustapha Chadjaa, Sanofi, Vitry-sur-Seine, France; Choung Soo Kim, Asan Medical Center, Seoul, South Korea; Lajos Géczi, National Institute of Oncology, Budapest, Hungary; Daniel Ford, City Hospital, Cancer Centre at Queen Elizabeth Hospital, Birmingham; Johann de Bono, Prostate Cancer Targeted Therapy Team, Royal Marsden National Health Service Foundation Trust/The Institute of Cancer Research, Sutton, United Kingdom; Joan Carles, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona; Phillip Parente, Eastern Health Clinical School, Monash University, Box Hill Hospital, Melbourne, Victoria, Australia; Albert Font, Institut Català d'Oncologia, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; Gabriel Kacso, Iuliu Hatieganu Medical University, Amethyst Radiology Therapeutic Center, Cluj, Romania; Wenping Zhang, Sanofi, Bridgewater, NJ; and John Bernard, Sanofi, Cambridge, MA.
J Clin Oncol. 2017 Oct 1;35(28):3198-3206. doi: 10.1200/JCO.2016.72.1076. Epub 2017 Aug 15.
Purpose Cabazitaxel 25 mg/m (C25) significantly improved overall survival (OS) versus mitoxantrone ( P < .001) in postdocetaxel patients with metastatic castration-resistant prostate cancer (mCRPC) in the phase III TROPIC study. The phase III PROSELICA study ( ClinicalTrials.gov identifier: NCT01308580) assessed the noninferiority of cabazitaxel 20 mg/m (C20) versus C25 in postdocetaxel patients with mCRPC. Methods Patients were stratified by Eastern Cooperative Oncology Group performance status, measurability of disease per Response Evaluation Criteria in Solid Tumors (RECIST), and region, and randomly assigned to receive C20 or C25. To claim noninferiority of C20 (maintenance of ≥ 50% of the OS benefit of C25 v mitoxantrone in TROPIC) with 95% confidence level, the upper boundary of the CI of the hazard ratio (HR) for C20 versus C25 could not exceed 1.214 under a one-sided 98.89% CI after interim analyses. Secondary end points included progression-free survival, prostate-specific antigen (PSA), tumor and pain responses and progression, health-related quality of life, and safety. Results Overall, 1,200 patients were randomly assigned (C20, n = 598; C25, n = 602). Baseline characteristics were similar in both arms. Median OS was 13.4 months for C20 and 14.5 months for C25 (HR, 1.024). The upper boundary of the HR CI was 1.184 (less than the 1.214 noninferiority margin). Significant differences were observed in favor of C25 for PSA response (C20, 29.5%; C25, 42.9%; nominal P < .001) and time to PSA progression (median: C20, 5.7 months; C25, 6.8 months; HR for C20 v C25, 1.195; 95% CI, 1.025 to 1.393). Health-related quality of life did not differ between cohorts. Rates of grade 3 or 4 treatment-emergent adverse events were 39.7% for C20 and 54.5% for C25. Conclusion The efficacy of cabazitaxel in postdocetaxel patients with mCRPC was confirmed. The noninferiority end point was met; C20 maintained ≥ 50% of the OS benefit of C25 versus mitoxantrone in TROPIC. Secondary efficacy end points favored C25. Fewer adverse events were observed with C20.
在多西他赛治疗后进展的转移性去势抵抗性前列腺癌（mCRPC）患者中，卡巴他赛 25mg/m（C25）显著改善了总生存期（OS），与米托蒽醌相比（P＜0.001），这在 III 期 TROPIC 研究中得到了证实。III 期 PROSELICA 研究（ClinicalTrials.gov 标识符：NCT01308580）评估了卡巴他赛 20mg/m（C20）与 C25 在多西他赛治疗后 mCRPC 患者中的非劣效性。
患者按东部肿瘤协作组体力状况、实体瘤反应评估标准（RECIST）的可测量性和区域分层，随机分配接受 C20 或 C25 治疗。为了声称 C20 的非劣效性（与 TROPIC 中米托蒽醌相比，C25 的 OS 获益维持≥50%），置信区间（CI）上限的 HR 为 1.214，95%CI 单侧为 98.89%，在中期分析后。次要终点包括无进展生存期、前列腺特异性抗原（PSA）、肿瘤和疼痛反应及进展、健康相关生活质量和安全性。
共随机分配了 1200 名患者（C20，n=598；C25，n=602）。两组的基线特征相似。C20 的中位 OS 为 13.4 个月，C25 为 14.5 个月（HR，1.024）。HR CI 的上限为 1.184（低于 1.214 的非劣效性边界）。C25 在 PSA 反应（C20，29.5%；C25，42.9%；名义 P＜0.001）和 PSA 进展时间（C20，5.7 个月；C25，6.8 个月；C20 与 C25 的 HR，1.195；95%CI，1.025 至 1.393）方面具有显著优势。两组间健康相关生活质量无差异。C20 组和 C25 组的 3 级或 4 级治疗相关不良事件发生率分别为 39.7%和 54.5%。
卡巴他赛在多西他赛治疗后进展的 mCRPC 患者中的疗效得到了证实。非劣效性终点得到满足；C20 维持了≥50%的 C25 与米托蒽醌在 TROPIC 中的 OS 获益。次要疗效终点有利于 C25。C20 组观察到的不良事件较少。
