Background: Questions about optimal sequencing of systemic agents in mCRPC and whether cross-resistance occurs between agents remain largely unanswered. Recently, it was reported that D is inactive in mCRPC pts who did not have a ≥ 50% PSA decline on prior AA (Ann Oncol 2012; 23(11):2943-7). To investigate this further, we evaluated the activity of D in mCRPC pts who had previously received AA. Methods: Cancer registries at two Canadian centers were used to identify mCRPC pts treated with D after AA. Outcomes from D treatment were compared between AA responders (≥ 50% PSA decrease with prior AA) and AA non-responders (< 50% PSA decrease with prior AA). Progression-free survival (PFS) (Prostate Cancer Working Group 2 criteria) and overall survival (OS) were estimated using the Kaplan-Meier method. Results: Of 40 eligible pts, 14 (35%) were classified as AA responders and 26 (65%) as AA non-responders (including 16 pts who had no PSA decline on AA). The median number of cycles of D administered to AA responders and non-responders was 6 (range: 1-10) and 4 (range: 1-13) respectively. Thirty (75%) pts had also received D prior to AA. Notably, among 39 pts evaluable for PSA response, no difference was seen in the proportion of AA responders and non-responders who had PSA falls ≥ 50% (p=0.72; Fisher’s exact test) or ≥ 30% (p=0.75; Fisher’s exact test) on D (Table). Analysis of survival outcomes from date of initiation of D also revealed similar median PFS (p=0.54; log-rank) and median OS (p=0.93; log-rank) in both groups (Table). Conclusions: PSA response rates to D did not differ between AA responders and non-responders. These data suggest that the anti-tumor activity of D in mCRPC may be independent of prior response to AA and that chemotherapy is still a therapeutic option in patients who do not respond to AA. Prospective studies evaluating optimal sequencing of AA and D in mCRPC are warranted.

Abbreviations: D, docetaxel; AA, abiraterone acetate.