Randomized phase II trial of Abiraterone alone or with Dasatinib in men with metastatic castration-resistant prostate cancer (mCRPC)

Abstract Background Signaling 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 Methods Eligible patients had mCRPC, without prior chemotherapy. Abiraterone was prescribed at 1000 mg daily with prednisone 5 mg BID in both arms and Dasatinib 100 mg daily was added for Arm B. The primary endpoint was PFS. Interim analysis was planned after 48 subjects but the study was terminated early. PFS was evaluated using a one-side logrank test. Fisher exact test was used for other categorical data analyses. Circulating tumor cells (CTC) were identified with the Epic platform. Results With 26 men were randomized and median follow up of 41.8 months, median PFS was 15.7 (95% CI: 8.2, 49.0+) months for Arm B and 9.0 (95% CI: 4.4, 30.7) months for Arm A (p=0.15). RECIST responses were seen in 5/14 (36%) including 2 CR on Arm B, and 2/12 responses (17%) without CR on Arm A (p=0.39). Grade > 3 toxicities more common in Arm B included hypertension, pleural effusion/dyspnea, and gastrointestinal effects. CTC were detected at baseline in 10/19 evaluable patients, median 2.7/mL blood (range 0.41-59.7). At week 4, CTC increased in 1/10 (10%) on Arm A and 4/9 (44%) on Arm B. Conclusion Dasatinib did not significantly prolong PFS in combination with Abiraterone, although power was limited due to incomplete study cohort. Treatment with the combination was associated with robust objective responses, including RECIST CRs.