Serum androgens and survival in metastatic castration resistant prostate cancer (mCRPC) patients treated with docetaxel and prednisone: Results from CALGB 90401 (Alliance).
Ryan, CJ; Dutta, S; Kelly, WK; Middleberg, R; Russell, C; Small, EJ; Morris, MJ; Taplin, M-E; Halabi, S
Published in: Journal of Clinical Oncology
5067 Background: Higher baseline androgens have been previously shown to be associated with an improved overall survival (OS) in mCRPC patients treated with the androgen synthesis inhibitors, ketoconazole or abiraterone. The purpose of this analysis was to determine whether baseline serum androgen levels (Testosterone (T), Androstenedione (A) and DHEA (D) are associated with OS in mCRPC patients treated with docetaxel-based chemotherapy. Methods: Data from 1,050 men treated on CALGB 90401 with docetaxel, prednisone and either bevacizumab or placebo were used. Eligibility required progressive mCRPC and no prior chemotherapy. Pre-treatment serum assays for T, A and D were performed via tandem Liquid Chromatography-Mass Spectrometry (LC-MS/MS) at NMS labs. The proportional hazards model was used to assess the prognostic significance of T, A, and D in predicting OS adjusting for known prognostic factors. Results: Median values for T, A, and, D were 1.00, 13.00 and 8.12, ng/dL respectively.Values above the median were defined as low, above as high. Median OS for low vs high levels was 22.7 and 23.1 month for T, 22.4 and 21.7 month for A and 21.8 and 24.0 month for D, respectively, all NS. In multivariable analysis adjusting for 10 known prognostic values and prior keto use in mCRPC (Halabi JCO 2014), A (p-value = 0.013) levels were associated with OS. The HR for A was = 0.99 (95% CI = 0.98-0.99). Conclusions: In multivariate analysis, baseline androstenedione levels are prognostic factors for OS in mCRPC patients receiving chemotherapy. Low or undetectable levels of other androgens are associated with shorter OS, consistent with prior results in androgen synthesis inhibitor treated pts in both the chemotherapy naive and post chemotherapy settings. This relationship may reflect more aggressive tumor biology that evolves in an extreme androgen deprived milieu. Clinical trial information: NCT00110214.
