Background

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).

Objective

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/m² plus prednisone and granulocyte colony-stimulating factor) versus abiraterone (1000 mg plus prednisone) or enzalutamide (160 mg).

Outcome measurements and statistical analysis

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.

Results and limitations

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.

Conclusions

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.

Patient summary

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.

中文翻译：

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CARD 研究中卡巴他赛与阿比特龙或恩杂鲁胺在老年转移性去势抵抗性前列腺癌患者中的疗效和安全性

背景

在 CARD 研究 (NCT02485691) 中，与阿比特龙/恩杂鲁胺相比，卡巴他赛显着改善了先前接受多西他赛治疗且进展≤ 12 个月使用替代药物（阿比特龙/恩杂鲁胺）。

客观的

评估卡巴他赛与阿比特龙/恩杂鲁胺在 CARD 中老年（≥70 岁）和年轻（<70 岁）患者中的疗效。

设计、设置和参与者

mCRPC 患者以 1:1 的比例随机分配至卡巴他赛（25 mg/m ²加强的松和粒细胞集落刺激因子）与阿比特龙（1000 mg 加强的松）或恩杂鲁胺（160 mg）组。

结果测量和统计分析

预先指定了按年龄划分的 rPFS（主要终点）和安全性分析；其他人是事后的。使用分层对数秩或 Cochran-Mantel-Haenszel 检验比较治疗组。

结果和局限性

在随机分配的 255 名患者中，135 名年龄≥70 岁（中位数为 76 岁）。与阿比特龙/恩杂鲁胺相比，卡巴他赛显着改善老年人（8.2 对 4.5 个月；风险比 [HR] = 0.58；95% 置信区间 [CI] = 0.38–0.89；p = 0.012）和更年轻（7.4 对 3.2）的中位 rPFS月；HR = 0.47；95% CI = 0.30–0.74；p < 0.001) 患者。在老年患者中，卡巴他赛与阿比特龙/恩杂鲁胺的中位 OS 分别为 13.9 个月和 9.4 个月（HR = 0.66；95% CI = 0.41-1.06；p = 0.084），年轻患者为 13.6 个月和 11.8 个月（HR = 0.66； 95% CI = 0.41–1.08；p = 0.093）。无论年龄大小，无进展生存期、前列腺特异性抗原、肿瘤和疼痛反应都偏爱卡巴他赛。与阿比特龙/恩杂鲁胺相比，接受卡巴他赛的老年患者与阿比特龙/恩杂鲁胺相比，58% 对 49% 的老年患者发生≥3 级治疗出现的不良事件 (TEAE)，在年轻患者中发生率为 48% 对 42%。在老年患者中，使用阿比特龙/恩杂鲁胺的心脏不良事件更常见；卡巴他赛组更容易出现乏力和腹泻。

结论

与阿比特龙/恩杂鲁胺相比，卡巴他赛在既往多西他赛和阿比特龙/恩杂鲁胺治疗后的 mCRPC 患者中改善了疗效结果，无论年龄大小。TEAE 在老年患者中更为常见。卡巴他赛的安全性分布在各个年龄组都是可控的。

患者总结

临床试验数据显示，与阿比特龙/恩杂鲁胺相比，卡巴他赛改善了既往接受多西他赛和替代药物（阿比特龙/恩杂鲁胺）治疗的转移性去势抵抗性前列腺癌患者的生存率，且副作用可控。