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

• Published in: European urology 2014-09, Vol.66 (3), p.459-465
• Main Authors: Pezaro, Carmel J, Omlin, Aurelius G, Altavilla, Amelia, Lorente, David, Ferraldeschi, Roberta, Bianchini, Diletta, Dearnaley, David, Parker, Christopher, de Bono, Johann S, Attard, Gerhardt
• Format: Article
• Language: English
• Subjects: Abiraterone; Androstenes - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Benzamides; Biological and medical sciences; Cabazitaxel; Castration-resistant prostate cancer; Disease Progression; Disease-Free Survival; Docetaxel; Enzalutamide; Gynecology. Andrology. Obstetrics; Humans; Male; Male genital diseases; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Nitriles; Phenylthiohydantoin - administration & dosage; Phenylthiohydantoin - analogs & derivatives; Prostate-Specific Antigen - blood; Prostatic Neoplasms, Castration-Resistant - blood; Prostatic Neoplasms, Castration-Resistant - drug therapy; Retreatment; Retrospective Studies; Survival Rate; Taxoids - administration & dosage; Treatment Failure; Treatment sequencing; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Urology
• ISSN: 0302-2838; 1873-7560
• DOI: 10.1016/j.eururo.2013.11.044

Abstract 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 next-generation 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 a median of 7 mo of abiraterone and 11 mo 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 abiraterone- and enzalutamide-naïve 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 drugs abiraterone and enzalutamide. Cabazitaxel appeared active when given after abiraterone and enzalutamide. We can reassure men that cabazitaxel can be used after these novel endocrine treatments.