BACKGROUND The efficacy and safety of cabazitaxel, as compared with an androgen-signaling-targeted inhibitor (abiraterone or enzalutamide), in patients with metastatic castration-resistant prostate cancer who were previously treated with docetaxel and had progression within 12 months while receiving the alternative inhibitor (abiraterone or enzalutamide) are unclear. METHODS We randomly assigned, in a 1:1 ratio, patients who had previously received docetaxel and an androgen-signaling-targeted inhibitor (abiraterone or enzalutamide) to receive cabazitaxel (at a dose of 25 mg per square meter of body-surface area intravenously every 3 weeks, plus prednisone daily and granulocyte colony-stimulating factor) or the other androgen-signaling-targeted inhibitor (either 1000 mg of abiraterone plus prednisone daily or 160 mg of enzalutamide daily). The primary end point was imaging-based progression-free survival. Secondary end points of survival, response, and safety were assessed. RESULTS A total of 255 patients underwent randomization. After a median follow-up of 9.2 months, imaging-based progression or death was reported in 95 of 129 patients (73.6%) in the cabazitaxel group, as compared with 101 of 126 patients (80.2%) in the group that received an androgen-signaling-targeted inhibitor (hazard ratio, 0.54; 95% confidence interval [CI], 0.40 to 0.73; P<0.001). The median imaging-based progression-free survival was 8.0 months with cabazitaxel and 3.7 months with the androgen-signaling-targeted inhibitor. The median overall survival was 13.6 months with cabazitaxel and 11.0 months with the androgen-signaling-targeted inhibitor (hazard ratio for death, 0.64; 95% CI, 0.46 to 0.89; P = 0.008). The median progression-free survival was 4.4 months with cabazitaxel and 2.7 months with an androgen-signaling-targeted inhibitor (hazard ratio for progression or death, 0.52; 95% CI, 0.40 to 0.68; P<0.001), a prostate-specific antigen response occurred in 35.7% and 13.5% of the patients, respectively (P<0.001), and tumor response was noted in 36.5% and 11.5% (P = 0.004). Adverse events of grade 3 or higher occurred in 56.3% of patients receiving cabazitaxel and in 52.4% of those receiving an androgen-signaling-targeted inhibitor. No new safety signals were observed. CONCLUSIONS Cabazitaxel significantly improved a number of clinical outcomes, as compared with the androgen-signaling-targeted inhibitor (abiraterone or enzalutamide), in patients with metastatic castration-resistant prostate cancer who had been previously treated with docetaxel and the alternative androgen-signaling-targeted agent (abiraterone or enzalutamide). (Funded by Sanofi; CARD ClinicalTrials.gov number, NCT02485691.).

中文翻译：

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卡巴他赛与阿比特龙或恩杂鲁胺在转移性前列腺癌中的关系。

背景：卡巴他赛与靶向雄激素信号的抑制剂（阿比特龙或恩杂鲁胺）相比，在转移性去势抵抗性前列腺癌患者中接受过多西他赛治疗且在接受替代抑制剂后12个月内进展，与之相比，其疗效和安全性（阿比特龙或恩杂鲁胺）尚不清楚。方法我们以1：1的比例将之前接受多西他赛和雄激素信号靶向抑制剂（阿比特龙或enzalutamide）的患者随机分配接受卡巴他赛（剂量为每平方米体表面积25 mg静脉注射）每3周加每天泼尼松和粒细胞集落刺激因子）或其他雄激素信号靶向抑制剂（每天1000 mg阿比特龙加泼尼松或每天160 mg enzalutamide）。主要终点是基于影像的无进展生存期。评估了生存，反应和安全性的次要终点。结果共有255例患者接受了随机分组。中位随访9.2个月后，卡巴他赛组中有129例患者中有95例（73.6％）报告了基于影像学的进展或死亡，而接受雄激素的126例患者中有101例（80.2％）信号靶向抑制剂（危险比，0.54； 95％置信区间[CI]，0.40至0.73； P <0.001）。卡巴他赛的中位影像学无进展生存期为8.0个月，雄激素信号靶向抑制剂为3.7个月。卡巴他赛的中位总生存期为13.6个月，雄激素信号靶向抑制剂的中位总生存期为11.0个月（死亡的危险比为0.64; 95％CI为0.46至0.89; P = 0。008）。使用卡巴他赛的中位无进展生存期为4.4个月，使用雄激素信号靶向抑制剂的中位无进展生存期为2.7个月（进展或死亡的危险比，0.52； 95％CI，0.40至0.68； P <0.001），一种前列腺特异性抗原分别在35.7％和13.5％的患者中出现了缓解（P <0.001），在36.5％和11.5％的患者中发现了肿瘤缓解（P = 0.004）。接受卡巴他赛的患者中有56.3％发生了3级或更高级别的不良事件，接受雄激素信号靶向抑制剂的患者中有52.4％发生了不良反应。没有观察到新的安全信号。结论与雄激素信号靶向抑制剂（阿比特龙或恩杂鲁胺）相比，卡巴他赛显着改善了许多临床结果，曾接受过多西他赛和其他雄激素信号靶向药物（阿比特龙或恩杂鲁胺）治疗的转移性去势抵抗性前列腺癌患者。（由赛诺菲资助； CARD ClinicalTrials.gov编号，NCT02485691。）。