title: Optimal sequencing of docetaxel and abiraterone in men with metastatic castration-resistant prostate cancer.
abstract: BACKGROUND
  Recent advances have yielded multiple new life-prolonging treatments for men with metastatic castration-resistant prostate cancer (mCRPC) including chemotherapy, next-generation hormonal therapy, immunotherapy, and radiopharmaceutical products. However, the optimal sequencing of these agents to maximize clinical benefit remains unclear. Recent data from the CHAARTED and STAMPEDE studies suggest that early use of docetaxel in men with metastatic hormone-sensitive prostate cancer (mHSPC) significantly improves survival, but whether early compared with delayed use of chemotherapy also provides a survival advantage in mCRPC is unknown.
  
  
  METHODS
  A retrospective analysis of consecutive mCRPC patients treated at Johns Hopkins is reported. Patients included were treated with sequential docetaxel and abiraterone, in either order. The combined progression-free survival (combined PFS: PFS1 + PFS2) of abiraterone-to-docetaxel is compared to the reverse sequence, where PFS1 and PFS2 represent progression-free survival on the first and second agents respectively. Overall survival (OS) from the start of the first therapy to death is compared between groups. Baseline characteristics are reported prior to the start of the first agent in the sequence. Propensity score-weighted multivariable models and Kaplan-Meier analysis are used for evaluation of the primary and secondary outcomes.
  
  
  RESULTS
  Fifty-eight patients who began treatment for mCRPC between January 2011 (the year of abiraterone's FDA-approval) and February 2015 were identified: 26 were in the docetaxel-to-abiraterone group and 32 were in the abiraterone-to-docetaxel group. Patients in the abiraterone-to-docetaxel group had more Gleason 8-10 tumors, greater metastatic burden in bone, and higher median PSAs than those in the docetaxel-to-abiraterone group. Propensity score-weighted univariate analyses for combined PFS (HR 0.82; 95%CI 0.50-1.33; P = 0.41) and OS (HR 0.79; 95%CI 0.50-1.25; P = 0.31) do not identify any significant differences based on treatment sequence. Propensity score-weighted multivariate analyses for combined PFS (HR 0.91; 95%CI 0.52-1.60; P = 0.74) and OS (HR 0.98; 95%CI 0.59-1.63; P = 0.95) also do not identify any significant differences between groups.
  
  
  CONCLUSIONS
  We do not observe differences in clinical outcomes based on alternative sequencing of abiraterone and docetaxel in men with mCRPC. Treatment sequencing should be determined by patient and disease characteristics, comorbidities and end-organ function, ability to tolerate side effects, and patient preferences. Studies evaluating biomarkers to inform optimal treatment sequencing in men with mCRPC are urgently needed.
authors: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.
authors: Benjamin L
authors: BL
authors: Maughan
authors: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.
authors: Xian C
authors: XC
authors: Xhou
authors: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.
authors: Daniel L
authors: DL
authors: Suzman
authors: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.
authors: Rosa
authors: R
authors: Nadal
authors: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.
authors: Sunakshi
authors: S
authors: Bassi
authors: Department of Medicine, Division of Oncology, University of Washington/Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Michael T
authors: MT
authors: Schweizer
authors: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.
authors: Emmanuel S
authors: ES
authors: Antonarakis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000736:Androstenes / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D018572:Disease-Free Survival; D000077143:Docetaxel; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D008875:Middle Aged; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000736:Androstenes; D043823:Taxoids; D000077143:Docetaxel; C089740:abiraterone
keywords: abiraterone; castration-resistant prostate cancer; docetaxel; sequencing