Activity of Cabazitaxel in Castration-resistant Prostate Cancer Progressing After Docetaxel and Next-generation Endocrine Agents

Background: Cabazitaxel, abiraterone, and enzalutamide are survival-prolonging treatments in men with castration-resistant prostate cancer (CRPC) progressing following docetaxel chemotherapy. The sequential activity of these agents has not been studied and treatment sequencing remains a key dilemma for clinicians. Objective: To describe the antitumour activity of cabazitaxel after docetaxel and nextgeneration endocrine agents. Design, setting, and participants: We report on a cohort of 59 men with progressing CRPC treated with cabazitaxel, 37 of whom had received prior abiraterone and 9 of whom had received prior enzalutamide. Outcome measurements and statistical analysis: Changes in prostate-specific antigen (PSA) level were used to determine activity on abiraterone, enzalutamide, and cabazitaxel treatment. Radiologic tumour regressions according to Response Evaluation Criteria in Solid Tumors (RECIST) and symptomatic benefit were evaluated for cabazitaxel therapy. Results and limitations: The post–endocrine-therapy patients received abiraterone (n = 32), sequential abiraterone and enzalutamide (n = 5) or enzalutamide (n = 4). These patients received amedian of 7 mo of abiraterone and 11mo of enzalutamide. A median of six cabazitaxel cycles (range: 1–10 cycles) were delivered, with 50% PSA declines in 16 of 41 (39%) patients, soft tissue radiologic responses in 3 of 22 (14%) evaluable patients, and symptomatic benefit in 9 of 37 evaluable patients (24%). Median overall survival and progression-free survival were 15.8 and 4.6 mo, respectively. Antitumor activity on cabazitaxel was less favourable in the abirateroneand enzalutamide-naı̈ve cohort (n = 18), likely reflecting biologic differences in this cohort. These data were obtained from a retrospective analysis. Conclusions: This is the first report of cabazitaxel activity in CRPC progressing after treatment with docetaxel and abiraterone or enzalutamide. We demonstrate significant cabazitaxel activity in this setting. Patient summary: We looked at the antitumour activity of the chemotherapy drug cabazitaxel in men previously treated with docetaxel chemotherapy and the hormonal nd enzalutamide. Cabazitaxel appeared active when given after lutamide. We can reassure men that cabazitaxel can be used after drugs abiraterone a abiraterone and enza these novel endocrine treatments. sociation of Urology. Published by Elsevier B.V. All rights reserved. # 2013 European As