Abstract 4153: Molecular profiling of circulating tumor cells (CTC) in patients with castrate resistant prostate cancer (CRPC) receiving abiraterone acetate (AA) after failure of docetaxel-based chemotherapy

Abstract

Abstract Background: Molecular profiles show consistent reactivation of AR in CRPC in part through overexpression of AR and of androgen-synthetic enzymes. AA inhibits CYP17 to decrease serum androgen to undetectable levels and was recently shown to confer a survival benefit for men with CRPC who have failed 1 or 2 chemotherapy regimens. Selecting targeted therapies in pts with CRPC remains a critical unmet need, where CTC are being tested as predictive biomarkers. The relevance of recurrent TMPRSS2:ERG rearrangement in CRPC remains poorly defined. Methods: AA (1000 mg QD PO) was studied in pts with CRPC who had progressed on docetaxel based chemotherapy. The primary endpoint was a ≥50% decline in PSA from baseline. Pre- and post-therapy CTC numbers were studied as response efficacy markers. The status AR and TMPRSS2:ERG was studied by FISH and multiplex RT-PCR, respectively, in enriched CTC. Results: 48 pts were treated, median (IQR) age was 73 years (63-79), PSA 99.9 ng/mL (36.4-343) and baseline CTC were 18 (4-49) per 7.5 ml of blood. Metastatic sites were bone alone in 10 pts, bone and lymph nodes in 21, 15 with visceral disease, and 2 with soft tissue alone. In 35 pts (73%) with ≥ 5 CTC at the start of treatment, 13 (37%, 95% CI 23-54%) pts had CTC decline to <5 after 1m of therapy; additionally 11/48 (23%, 95% CI 13-37%) pts had CTC <5 at all times (group A). CTC remained ≥ 5 in 22/48 (46%, 95% CI 33-60%) pts and 2/48 (4%, 95% CI 1-14%) pts had an increase of CTC from <5 to ≥ 5 (group B). Pts in Group A had a median time to PSA progression of 28 weeks, compared to 12 weeks in group B (P <0.005). From 28 pts with FISH in CTC, 5/19 pts with AR amplification or gain had a decrease in PSA with AA; 5/9 pts with no abnormality detected showed a significant decline in PSA. TMPRSS2:ERG was detected in 15/41 pts (37%), of which 7 (47%) pts had >50% PSA decline compared to 10/26 (38%) of pts without TMPRSS2:ERG. Conclusions: The significant relationship between clinical outcomes and changes in CTC number as biomarker of response efficacy warrants further testing in multiple prospective phase 3 trials. In this dataset, TMPRSS2:ERG status did not predict for changes in PSA. Additional follow up will be needed to explore associations with other clinical outcomes. Supported by: NCI SPORE in Prostate Cancer (P50 CA92629); Prostate Cancer Foundation; Mr. William H. Goodwin and Mrs. Alice Goodwin and the Commonwealth Foundation for Cancer Research, The Experimental Therapeutics Center of Memorial Sloan-Kettering Cancer Center; Department of Defense PCRP PC081051. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4153. doi:10.1158/1538-7445.AM2011-4153