Randomized Phase II Trial of Abiraterone Alone or With Dasatinib in Men With Metastatic Castration-resistant Prostate Cancer (mCRPC).

backgroundSignaling via the Src pathway is thought to be a mediator of resistance to androgen targeted therapy in prostate cancer. We studied whether adding the Src inhibitor dasatinib to abiraterone would delay progression. PATIENTS AND

methodsEligible patients had metastatic castration-resistant prostate cancer (mCRPC), without prior chemotherapy. Abiraterone was prescribed at 1000 mg daily with prednisone 5 mg twice daily in both arms, and dasatinib 100 mg daily was added for Arm B. The primary endpoint was progression-free survival (PFS). The interim analysis was planned after 48 subjects, but the study was terminated early. PFS was evaluated using a 1-sided log rank test. The Fisher exact test was used for other categorical data analyses. Circulating tumor cells (CTCs) were identified with the Epic platform.

resultsWith 26 men randomized and a median follow up of 41.8 months, the median PFS was 15.7 months (95% confidence interval, 8.2-49.0+ months) for Arm B and 9.0 months (95% confidence interval, 4.4-30.7 months) for Arm A (P = .15). Response Evaluation Criteria in Solid Tumors responses were seen in 5 (36%) of 14 patients, including 2 complete responses (CRs) on Arm B, and 2 (17%) of 12 responses without CR on Arm A (P = .39). Grade ≥ 3 toxicities more common in Arm B included hypertension, pleural effusion/dyspnea, and gastrointestinal effects. CTCs were detected at baseline in 10 of 19 evaluable patients (median, 2.7/mL blood [range 0.41-59.7]). At week 4, CTCs increased in 1 (10%) of 10 patients on Arm A and 4 (44%) of 9 patients on Arm B.

conclusionDasatinib did not significantly prolong PFS in combination with abiraterone, although power was limited owing to the incomplete study cohort. Treatment with the combination was associated with robust objective responses, including Response Evaluation Criteria in Solid Tumors CRs.