Englander Institute for Precision Medicine, Weill Cornell Medicine, Meyer Cancer Center, New York, NY, USA.
12 de Octubre University Hospital, Madrid, Spain.
Eur Urol. 2021 Oct;80(4):497-506. doi: 10.1016/j.eururo.2021.06.021. Epub 2021 Jul 15.
In the CARD study (NCT02485691), cabazitaxel significantly improved median radiographic progression-free survival (rPFS) and overall survival (OS) versus abiraterone/enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who had previously received docetaxel and progressed ≤12 mo on the alternative agent (abiraterone/enzalutamide).
To assess cabazitaxel versus abiraterone/enzalutamide in older (≥70 yr) and younger (<70 yr) patients in CARD.
DESIGN, SETTING, AND PARTICIPANTS: Patients with mCRPC were randomized 1:1 to cabazitaxel (25 mg/m plus prednisone and granulocyte colony-stimulating factor) versus abiraterone (1000 mg plus prednisone) or enzalutamide (160 mg).
Analyses of rPFS (primary endpoint) and safety by age were prespecified; others were post hoc. Treatment groups were compared using stratified log-rank or Cochran-Mantel-Haenszel tests.
Of the 255 patients randomized, 135 were aged ≥70 yr (median 76 yr). Cabazitaxel, compared with abiraterone/enzalutamide, significantly improved median rPFS in older (8.2 vs 4.5 mo; hazard ratio [HR] = 0.58; 95% confidence interval [CI] = 0.38-0.89; p = 0.012) and younger (7.4 vs 3.2 mo; HR = 0.47; 95% CI = 0.30-0.74; p < 0.001) patients. The median OS of cabazitaxel versus abiraterone/enzalutamide was 13.9 versus 9.4 mo in older patients (HR = 0.66; 95% CI = 0.41-1.06; p = 0.084), and it was 13.6 versus 11.8 mo in younger patients (HR = 0.66; 95% CI = 0.41-1.08; p = 0.093). Progression-free survival, prostate-specific antigen, and tumor and pain responses favored cabazitaxel, regardless of age. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 58% versus 49% of older patients receiving cabazitaxel versus abiraterone/enzalutamide and 48% versus 42% of younger patients. In older patients, cardiac adverse events were more frequent with abiraterone/enzalutamide; asthenia and diarrhea were more frequent with cabazitaxel.
Cabazitaxel improved efficacy outcomes versus abiraterone/enzalutamide in patients with mCRPC after prior docetaxel and abiraterone/enzalutamide, regardless of age. TEAEs were more frequent among older patients. The cabazitaxel safety profile was manageable across age groups.
Clinical trial data showed that cabazitaxel improved survival versus abiraterone/enzalutamide with manageable side effects in patients with metastatic castration-resistant prostate cancer who had previously received docetaxel and the alternative agent (abiraterone/enzalutamide), irrespective of age.
在 CARD 研究（NCT02485691）中，与阿比特龙/恩扎卢胺相比，卡巴他赛显著改善了转移性去势抵抗性前列腺癌（mCRPC）患者的中位影像学无进展生存期（rPFS）和总生存期（OS），这些患者之前接受过多西他赛治疗，并且在替代药物（阿比特龙/恩扎卢胺）治疗后 12 个月内进展。
评估 CARD 中年龄较大（≥70 岁）和年龄较小（<70 岁）患者中卡巴他赛与阿比特龙/恩扎卢胺的疗效。
设计、地点和参与者：将 mCRPC 患者按 1:1 随机分配至卡巴他赛（25mg/m 联合泼尼松和粒细胞集落刺激因子）与阿比特龙（1000mg 联合泼尼松）或恩扎卢胺（160mg）。
rPFS（主要终点）和安全性的分析按年龄预先设定；其他为事后分析。使用分层对数秩或 Cochran-Mantel-Haenszel 检验比较治疗组。
在 255 名随机患者中，135 名年龄≥70 岁（中位年龄 76 岁）。与阿比特龙/恩扎卢胺相比，卡巴他赛显著改善了年龄较大（8.2 与 4.5 个月；风险比[HR]0.58；95%置信区间[CI]0.38-0.89；p=0.012）和年龄较小（7.4 与 3.2 个月；HR0.47；95%CI0.30-0.74；p<0.001）患者的中位 rPFS。与阿比特龙/恩扎卢胺相比，卡巴他赛与阿比特龙/恩扎卢胺的中位 OS 分别为 13.9 个月与 9.4 个月（HR0.66；95%CI0.41-1.06；p=0.084），在年龄较小的患者中分别为 13.6 个月与 11.8 个月（HR0.66；95%CI0.41-1.08；p=0.093）。无论年龄大小，无进展生存期、前列腺特异性抗原、肿瘤和疼痛反应均有利于卡巴他赛。卡巴他赛组和阿比特龙/恩扎卢胺组≥3 级治疗相关不良事件（TEAEs）发生率分别为 58%和 49%（年龄较大的患者）和 48%和 42%（年龄较小的患者）。在年龄较大的患者中，阿比特龙/恩扎卢胺组心脏不良事件更为常见；卡巴他赛组乏力和腹泻更为常见。
无论年龄大小，与阿比特龙/恩扎卢胺相比，卡巴他赛在先前接受过多西他赛和阿比特龙/恩扎卢胺治疗的 mCRPC 患者中提高了疗效。年龄较大的患者中 TEAEs 更为常见。卡巴他赛的安全性在各年龄组均可控。
临床试验数据显示，在先前接受过多西他赛和替代药物（阿比特龙/恩扎卢胺）治疗的转移性去势抵抗性前列腺癌患者中，与阿比特龙/恩扎卢胺相比，卡巴他赛改善了生存，且副作用可管理。
