title: Activity of cabazitaxel in castration-resistant prostate cancer progressing after docetaxel and next-generation endocrine agents.
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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  RESULTS
  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.
authors.affiliation: Prostate Cancer Targeted Therapy Group and Academic Urology Unit, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Carmel J
authors.initials: CJ
authors.lastname: Pezaro
authors.affiliation: Prostate Cancer Targeted Therapy Group and Academic Urology Unit, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Aurelius G
authors.initials: AG
authors.lastname: Omlin
authors.affiliation: Prostate Cancer Targeted Therapy Group and Academic Urology Unit, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Amelia
authors.initials: A
authors.lastname: Altavilla
authors.affiliation: Prostate Cancer Targeted Therapy Group and Academic Urology Unit, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: David
authors.initials: D
authors.lastname: Lorente
authors.affiliation: Prostate Cancer Targeted Therapy Group and Academic Urology Unit, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ferraldeschi
authors.affiliation: Prostate Cancer Targeted Therapy Group and Academic Urology Unit, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Diletta
authors.initials: D
authors.lastname: Bianchini
authors.affiliation: Prostate Cancer Targeted Therapy Group and Academic Urology Unit, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: David
authors.initials: D
authors.lastname: Dearnaley
authors.affiliation: Prostate Cancer Targeted Therapy Group and Academic Urology Unit, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Parker
authors.affiliation: Prostate Cancer Targeted Therapy Group and Academic Urology Unit, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Johann S
authors.initials: JS
authors.lastname: de Bono
authors.affiliation: Prostate Cancer Targeted Therapy Group and Academic Urology Unit, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, Surrey, UK. Electronic address: gerhardt.attard@icr.ac.uk.
authors.forename: Gerhardt
authors.initials: G
authors.lastname: Attard
mesh_terms: D000736:Androstenes / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides; D018450:Disease Progression; D018572:Disease-Free Survival; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000008:administration & dosage / Q000031:analogs & derivatives; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy*; D019233:Retreatment; D012189:Retrospective Studies; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage*; D017211:Treatment Failure
chemical_list: D000736:Androstenes; D001549:Benzamides; D009570:Nitriles; D043823:Taxoids; D000077143:Docetaxel; D010669:Phenylthiohydantoin; C552428:cabazitaxel; C540278:enzalutamide; D017430:Prostate-Specific Antigen; C089740:abiraterone
keywords: Abiraterone; Cabazitaxel; Castration-resistant prostate cancer; Enzalutamide; Treatment sequencing