Circulating tumor cells (CTC) in patients with metastatic castration-resistant prostate cancer (CRPC) receiving abiraterone acetate (AA) after failure of docetaxel-based chemotherapy

Abstract

5049 Background: Selecting targeted therapies and assessing outcome in patients (pts) with CRPC are significant unmet medical needs. A proportion of CRPC remain dependent on androgen receptor (AR) activation. AA inhibits CYP17 to decrease serum androgen to undetectable levels. Methods: AA (1000 mg QD oral) was studied in pts with metastatic CRPC who had progressed on docetaxel based chemotherapy. The primary endpoint was a >50% decline in PSA from baseline. We monitored changes in CTC number with therapy, and performed FISH for AR in CTC as previously described. Results: At MSKCC, 54 pts were screened and 48 treated; 38 pts received prednisone from the start of treatment. The median (IQR) age was 70 yrs (63–79), PSA 99.9 ng/mL (36.4–343), and CTC were 17 (4–49) per 7.5 ml of blood at baseline. Prior systemic therapy included > 3 hormonal therapies in 63%; while 71% received 1, 29% had 2 lines of chemotherapy. Metastatic sites were bone alone in 10 pts (21%), bone and lymph nodes in 21 (44%), 15 (31%) with visceral disease, 2 with soft tissue alone. Baseline CTC count was > 5 in 35 pts, whereas 13 pts had <5; CTC changes with treatment are presented in table below. Pts in Group A were treated on protocol for a median of 8.9 m, compared to 2.8 m in group B (P <0.001). Among pts with baseline CTC > 5, the CTC decline to <5 was associated with a decline in PSA by >50% (p< 0.001). From 28 pts with FISH in CTC, 13 (47%) pts had AR amplification, 8 (29%) pts had copy number gain, and 5 (10%) pts had no evident AR copy number abnormalities; FISH failed in 2 pts. PSA declined > 50% in 5 (38%) pts with AR amplification, 2 (25%) pts with gain, and 4 (80%) pts without AR abnormalities. Conclusions: Changes in CTC with treatment may represent valuable intermediary endpoints for clinical benefit. We are prospectively testing pre and post-therapy CTC, and separately AR FISH profiles and clinical outcomes in COU-AA-301, a phase III trial for CRPC patients who have received docetaxel based chemotherapy. [Table: see text] [Table: see text]