Evaluating the value of continuing docetaxel and prednisone (DP) beyond 10 cycles in men with metastatic castration-resistant prostate cancer (mCRPC).
4582 Background: The optimal number of cycles of 3-weekly DP therapy for mCRPC has not been ascertained. An exploratory analysis was conducted comparing results of 335 men on the DP arm of the TAX-327 study, which limited chemotherapy to 10 cycles, and a recently completed randomized clinical trial of 221 men allocated to either DP+AT-101 (bcl-2 inhibitor) versus DP+placebo, which allowed up to 17 cycles of DP. METHODS: Patients who initiated cycle 10 of therapy without progression in both studies were included. Per protocol, men on the TAX-327 study received 1 additional cycle, while men on the AT-101 study received up to cycle 17. Men in both arms of the AT-101 study were combined for analysis, as no significant differences in outcomes were observed. Overall survival (OS) was estimated from the cycle 10 D infusion date, using the Kaplan-Meier method. RESULTS: The number of men receiving cycle 10 cycle was similar (Fisher's exact test p-value=0.60) between the two studies (166 or 49.6% in the TAX-327 study versus 99 or 44.8% in the AT-101 study), though of these men, death date information was more complete due to longer follow-up in TAX-327 (79.5% versus 34.4%). Six- and 12-month estimated survival from cycle 10 was 92.2% (95% CI: 86.9-95.4%) and 74.6% (CI: 67.2-80.5%) for TAX-327 patients, compared with 92.8% (CI: 85.5-96.5) and 63.4% (CI: 51.8-72.9%) for those on AT-101. Survival statistics were similar beyond cycle 10 within good, intermediate and poor risk groups. 38 (38.4%) men on the AT-101 study completed all 17 cycles. Of men on the AT-101 study, 24 and 13 had consistently declining PSA through cycles 13 and 17. CONCLUSIONS: A survival benefit was not detected with more than 10 cycles of DP chemotherapy in men with mCRPC in this hypothesis-generating exploratory analysis. A subset of men with mCRPC continue to have declines in PSA up to cycle 17 and thus may have ongoing benefit to continued chemotherapy administration. However, a randomized clinical trial is necessary to establish the optimal duration of therapy.
Pond, GR; Armstrong, AJ; Wood, BA; Brookes, M; Leopold, LH; Berry, WR; De Wit, R; Eisenberger, MA; Tannock, I; Sonpavde, G
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