925P - Clinical activity of abiraterone acetate (AA) after progression on mdv3100 in patients with metastatic castration resistant prostate cancer (mCRPC)

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Anti-Cancer Agents & Biologic Therapy
Prostate Cancer
Presenter Krista Noonan
Authors K. Noonan1, S. Ellard2, K.N. Chi3
  • 1British Columbia Cancer Agency, V5Z 4E6 - Vancouver/CA
  • 2Medical Oncology, BC Cancer Agency - Centre for the Southern Interior, V1Y5L3 - Kelowna/CA
  • 3Oncology, Vancouver Cancer Centre, University of British Columbia, V5Z 1L3 - Vancouver/CA

Abstract

Background

AA improves outcomes in patients with mCRPC through inhibition of CYP17 and androgen synthesis. Recently MDV3100, an androgen receptor antagonist has also been shown to improve overall survival from mCRPC in patients progressing after docetaxel. The optimal sequencing for these agents and whether induction of cross-resistance occurs is unknown.

Methods

Multi-centre retrospective review of all patients with mCRPC treated with AA after progressing on MDV3100.

Results

25 patients were identified from 3 centres in Canada. Baseline characteristics at time of AA initiation included a median age of 72 years, metastases in bone, lymph nodes and lung/liver were present in 88, 44 and 28% respectively, 36% of patients were on opiates, median hemoglobin was 120 g/L, median alkaline phosphatase was 144 U/L, and LDH was elevated in 28%. 100% had prior docetaxel chemotherapy and 0% prior ketoconazole. Median duration of prior MDV3100 was 34 weeks (range 8-95), with 64% (16/25) having had a >30% decline in PSA and 32% (8/25) having a rising PSA as best response. After AA, 21 patients were evaluable for response. The median duration of treatment with AA was 12 weeks (range 0-80). 14% (3/21) had a >30% PSA decline. Of these 3 patients, 1 continues to respond at 84 weeks of follow-up, while the other 2 had a time to PSA progression (defined as a 25% increase from nadir and a minimum of 2ug/mL) of 18, and 21 weeks. Interestingly, the 2 patients with PSA responses of 18 and 21 weeks on AA did not respond to MDV3100. 81% (17/21) had a rising PSA as best response. No objective responses were observed. Median time to progression (PSA, objective or symptomatic) on AA was 14.6 weeks [CI 8.8-20.4] and median overall survival was 48.7 weeks.

Conclusions

In this study of patients progressing after MDV3100, treatment with AA was associated with a modest response rate; however primary resistance to MDV3100 may not preclude a response to AA. The clinical activity of MDV3100 after progression on AA should also be evaluated to assist in the determination of the optimal sequencing of these agents.

Disclosure

All authors have declared no conflicts of interest.