Evaluating the safety of abiraterone acetate (AA) and docetaxel (D) administered in combination in patients (Pts) with metastatic castration-resistant prostate cancer (mCRPC).
205 Background: D and AA may have complementary mechanisms of action; coadministration may be beneficial. A phase Ib study assesses the safety of escalating doses of D + AA. Methods: Up to4 cohorts (C) of chemo-naïve mCRPC pts would receive D + AA. Data for C1 and C2 are presented. Primary end point: proportion of pts with dose-limiting toxicity (DLT) between Wks 2 and 7, defined as grade (Gr) ≥ 3 non-heme toxicity, Gr 4 neutropenia (absolute neutrophil count < 500/mm3) > 7 days (or febrile neutropenia), Gr 4 thrombocytopenia, or other intolerable toxicity. D + AA was deemed safe if ≤ 33% of pts experienced DLT. Pharmacokinetic (PK) parameters were evaluated for D and AA alone and in combination. Results: 15 pts were treated and 6 pts/C were evaluable for DLT assessment. 2 DLTs were observed in C1, and 1 in C2. 73% and 87% of pts had confirmed ≥ 90% and ≥ 50% prostate-specific antigen (PSA) decline, respectively. Median time to PSA progression has not yet been reached. Systemic exposure, based on maximum plasma concentration (Cmax) and area under the concentration–time curve [(AUC)∞ for D, AUC24 for abiraterone (ABI)], was comparable for both D and AA alone and for D + AA. 3 pts in C3 (D 75 mg/m2+ AA 1000 mg) have been treated past Wk 7 without DLT. Conclusions: D + AA was well tolerated in the cohorts tested. Preliminary results justify further evaluation of safety and efficacy in additional Cs. Clinical trial information: NCT01400555. [Table: see text]