title: Clinical activity of enzalutamide versus docetaxel in men with castration-resistant prostate cancer progressing after abiraterone.
abstract: BACKGROUND
  The optimal sequencing of the multiple active agents now available for metastatic castration-resistant prostate cancer (mCRPC) is unclear. Prior reports have suggested diminished responses to sequential lines of androgen receptor (AR)-targeted therapies, but it is unknown whether subsequent taxane-based chemotherapy may be more effective than sequential AR-targeting treatment. We sought to evaluate the clinical activity of enzalutamide versus docetaxel in men with mCRPC who progressed on abiraterone.
  
  
  METHODS
  We performed a single-institution retrospective analysis of consecutive mCRPC patients who had progressed on abiraterone therapy and subsequently received either enzalutamide (n=30) or docetaxel (n=31). We evaluated clinical outcomes including prostate-specific antigen decline of >30% (PSA30) or >50% (PSA50), PSA-progression-free survival (PSA-PFS), and clinical/radiographic PFS. We performed multivariable modeling to control for baseline and on-treatment differences between groups.
  
  
  RESULTS
  Compared to subjects who received enzalutamide post-abiraterone, subjects who received docetaxel post-abiraterone had more bone metastases, more visceral metastases, higher baseline PSA, and had more frequent PSA tests while on-treatment. There were no significant differences in PSA30 (41% for enzalutamide vs. 53% for docetaxel) or PSA50 (34% vs. 40%) response rates between the two groups; there remained no difference after stratifying by presence/absence of prior response to abiraterone. Median PSA-PFS was 4.1 versus 4.1 months for the enzalutamide and docetaxel cohorts, respectively (HR 1.35, 95% CI, 0.53-3.66, P=0.502). Median PFS was 4.7 versus 4.4 months, respectively (HR 1.44, 95% CI, 0.77-2.71, P=0.257). PSA-PFS and PFS did not differ after stratifying by prior response to abiraterone. In multivariable analyses, there were no significant differences in PSA-PFS or PFS between the two groups.
  
  
  CONCLUSIONS
  Treatment with either enzalutamide or docetaxel produced modest PSA responses and PFS intervals in this abiraterone-pretreated mCRPC population. In this retrospective study with small sample size, no significant differences in outcomes were observed between groups. Therefore, either enzalutamide or docetaxel may be a reasonable option in men who have progressed on abiraterone.
authors: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
authors: Daniel L
authors: DL
authors: Suzman
authors: Brandon
authors: B
authors: Luber
authors: Michael T
authors: MT
authors: Schweizer
authors: Rosa
authors: R
authors: Nadal
authors: Emmanuel S
authors: ES
authors: Antonarakis
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000368:Aged; D000736:Androstenes; D000737:Androstenols / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D018450:Disease Progression; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D012189:Retrospective Studies; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000736:Androstenes; D000737:Androstenols; D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D043823:Taxoids; D000077143:Docetaxel; D010669:Phenylthiohydantoin; C540278:enzalutamide; C089740:abiraterone
keywords: abiraterone; docetaxel; enzalutamide; prostate cancer; sequencing