title: Outcomes with abiraterone acetate in metastatic castration-resistant prostate cancer patients who have poor performance status.
abstract: BACKGROUND
  Although abiraterone acetate (abiraterone) has proven efficacy in two randomised phase 3 trials in metastatic castration-resistant prostate cancer (mCRPC), patients who had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2 were either excluded or under-represented in these trials.
  
  
  OBJECTIVE
  To compare outcomes in ECOG PS 0-1 and ≥2 in mCRPC patients treated with abiraterone.
  
  
  METHODS
  Cancer registries from three Canadian centres were used to retrospectively identify mCRPC patients (postdocetaxel and docetaxel-naïve) treated with abiraterone. ECOG PS, clinicopathologic characteristics, prostate-specific antigen (PSA) response, and survival data were collected.
  
  
  METHODS
  Survival outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards modelling was used to examine the effect of clinicopathologic characteristics on overall survival (OS) and time to PSA progression.
  
  
  CONCLUSIONS
  A total of 519 patients were identified; 61% (n=318) and 39% (n=201) were ECOG PS 0-1 and ≥2, respectively. ECOG PS 0-1 patients were significantly more likely than PS ≥2 patients to achieve a PSA decline ≥50% from baseline (45% vs 32%; p=0.003, Fisher exact test) and had significantly longer median time to PSA progression (5.2 mo vs 4.1 mo; p=0.023), median treatment duration (7.4 mo vs 4.5 mo; p<0.001), and median OS (20.0 mo vs 9.1 mo; p<0.001). On multivariate analysis, ECOG PS was a significant factor for OS (p<0.001), time to PSA progression (p=0.043), and PSA decline (p=0.002). Potential limitations include the retrospective study design and subjective nature of ECOG PS classification.
  
  
  CONCLUSIONS
  ECOG PS ≥2 mCRPC patients treated with abiraterone have inferior outcomes compared with ECOG 0-1 patients, especially in regard to OS. These data indicate that early initiation of abiraterone prior to a decline in PS may be warranted.
  
  
  RESULTS
  We found that advanced prostate cancer patients who have worse performance status (PS) derive less benefit from abiraterone, indicating that earlier treatment before PS declines could improve outcomes.
authors: Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors: Arun A
authors: AA
authors: Azad
authors: Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors: Bernhard J
authors: BJ
authors: Eigl
authors: Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
authors: Raya
authors: R
authors: Leibowitz-Amit
authors: Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada.
authors: Renee
authors: R
authors: Lester
authors: Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors: Christian
authors: C
authors: Kollmannsberger
authors: Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors: Nevin
authors: N
authors: Murray
authors: Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada.
authors: Ravinder
authors: R
authors: Clayton
authors: Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada.
authors: Daniel Y C
authors: DY
authors: Heng
authors: Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
authors: Anthony M
authors: AM
authors: Joshua
authors: Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada. Electronic address: kchi@bccancer.bc.ca.
authors: Kim N
authors: KN
authors: Chi
mesh_terms: D000069501:Abiraterone Acetate / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D002170:Canada; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D006304:Health Status; D006801:Humans; D007610:Kallikreins / Q000097:blood; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009376:Neoplasms, Hormone-Dependent / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D012189:Retrospective Studies; D012307:Risk Factors; D065088:Steroid Synthesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D065607:Cytochrome P-450 Enzyme Inhibitors; D065088:Steroid Synthesis Inhibitors; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen; D000069501:Abiraterone Acetate
keywords: Abiraterone acetate; Castration-resistant prostate cancer; ECOG; Performance status; Prostate cancer