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转移性去势抵抗性前列腺癌中卡巴他赛的真实世界应用及结局:首次抗雄激素药物治疗反应的影响。

Real-World Cabazitaxel Use and Outcomes in Metastatic Castrate-Resistant Prostate Cancer: The Impact of Response to First ARPI.

机构信息

Department of Oncology, University of Calgary, Tom Baker Cancer Centre, Calgary, AB, Canada.

Department of Oncology, University of Calgary, Tom Baker Cancer Centre, Calgary, AB, Canada.

出版信息

Clin Genitourin Cancer. 2022 Oct;20(5):496.e1-496.e9. doi: 10.1016/j.clgc.2022.04.009. Epub 2022 Apr 26.

Abstract

BACKGROUND

For post-docetaxel treatment of metastatic castrate-resistant prostate cancer (mCRPC), cabazitaxel has demonstrated superior third line PFS and OS compared to androgen receptor pathway inhibitors (ARPIs) in patients who progress within 12 months on first ARPI. The impact of first ARPI response, in particular responses beyond 12 months, on cabazitaxel outcomes in real-world populations is uncertain, as are other factors impacting cabazitaxel use.

MATERIALS AND METHODS

mCRPC patients in Alberta, Canada who received docetaxel from October 1, 2012 to December 31, 2017 were included. We reviewed mCRPC therapies, correlating cabazitaxel use with patient characteristics and TROPIC trial inclusion/exclusion criteria. OS and PFS were evaluated in patients who received cabazitaxel, stratified by time to progression on first ARPI ≤ 12 months (poor ARPI responders, PAR) or >12 months (strong ARPI responders, SAR), using the Kaplan-Meier method.

RESULTS

PAR patients had inferior OS compared to SAR patients (12.3 vs. 24.8 months, P < .001). OS was longer in PAR patients receiving cabazitaxel compared to those not treated with cabazitaxel (16.9 vs. 10.3 months, P = .015), but this benefit was not seen in the SAR group (17.1 vs. 32 months, P = .084). Cabazitaxel use was associated with reduced PFS first line post-docetaxel in SAR (3.5 vs. 14.7 months, P < .001) but not PAR patients. Of 592 patients, 170 (29%) received cabazitaxel post-docetaxel, compared to 280 (47%) and 250 (42%) for abiraterone and enzalutamide. 238 patients (40%) did not have a discussion of cabazitaxel documented. Cabazitaxel use was increased in patients who fit TROPIC trial criteria (P < .001).

CONCLUSIONS

In a real-world mCRPC cohort, cabazitaxel use was associated with longer OS among PAR patients, but crucially not among strong ARPI responders. Cabazitaxel was used less frequently and later than ARPIs post-docetaxel. These data help support first ARPI progression time as a consideration in treatment sequencing.

摘要

背景

对于多西他赛治疗后的转移性去势抵抗性前列腺癌(mCRPC)患者,在接受第一代雄激素受体通路抑制剂(ARPI)治疗 12 个月内进展的患者中,卡巴他赛在第三线无进展生存期(PFS)和总生存期(OS)方面优于 ARPI。在真实世界人群中,首次 ARPI 反应(特别是 12 个月后)对卡巴他赛结局的影响以及其他影响卡巴他赛使用的因素尚不确定。

材料和方法

纳入 2012 年 10 月 1 日至 2017 年 12 月 31 日期间在加拿大阿尔伯塔省接受多西他赛治疗的 mCRPC 患者。我们回顾了 mCRPC 治疗方法,并将卡巴他赛的使用与患者特征和 TROPIC 试验纳入/排除标准相关联。在接受卡巴他赛治疗的患者中,根据首次 ARPI 进展时间(≤12 个月,即差的 ARPI 反应者,PAR;>12 个月,即强的 ARPI 反应者,SAR),使用 Kaplan-Meier 方法评估 OS 和 PFS。

结果

PAR 患者的 OS 明显差于 SAR 患者(12.3 个月 vs. 24.8 个月,P<0.001)。与未接受卡巴他赛治疗的患者相比,PAR 患者接受卡巴他赛治疗后的 OS 更长(16.9 个月 vs. 10.3 个月,P=0.015),但 SAR 组未观察到这种获益(17.1 个月 vs. 32 个月,P=0.084)。SAR 患者接受卡巴他赛治疗后,一线多西他赛治疗后的 PFS 明显缩短(3.5 个月 vs. 14.7 个月,P<0.001),但在 PAR 患者中未观察到这种获益。在 592 名患者中,170 名(29%)接受了卡巴他赛治疗,而接受阿比特龙和恩杂鲁胺治疗的患者分别为 280 名(47%)和 250 名(42%)。238 名患者(40%)没有记录卡巴他赛的讨论。卡巴他赛的使用在符合 TROPIC 试验标准的患者中增加(P<0.001)。

结论

在真实世界的 mCRPC 队列中,卡巴他赛的使用与 PAR 患者的 OS 延长有关,但在强 ARPI 反应者中并无明显获益。卡巴他赛的使用在多西他赛治疗后较 ARPI 更为少见且更晚。这些数据有助于支持首次 ARPI 进展时间作为治疗顺序的考虑因素。

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