Predictive associations between serum oxo-androgens, race, and radiographic progression-free survival (rPFS) among patients treated with apalutamide (Apa), abiraterone acetate (AA) plus prednisone (P) in the PANTHER study.

Abstract

247 Background: Prior studies have demonstrated that the hormonal environment in which prostate cancer develops may predict for sensitivity to Androgen Receptor pathway inhibition (ARPI). We hypothesized that high levels of serum 11-oxygenated androgens, a group of potent adrenal-derived steroids, might predict for better AR pathway targeting . We analyzed baseline serum androgens, including the oxo-androgens 11-OH testosterone (11-OHT), and 11-ketotestosterone (11-KT) from patients in two studies: (1) PANTHER, a prospective trial of Black and White cohorts of metastatic castration-resistant prostate cancer (mCRPC) patients treated with dual ARPI Apa and AA + P and (2) Abi Race, a similar prospective study of mCRPC patients treated with AA + P. We explored baseline androgen levels and their association with radiographic progression-free survival (rPFS) in each study and by race. Methods: We measured levels of 12 steroid hormones using liquid chromatography-tandem mass spectrometry in serum samples obtained at baseline from 161 of the 193 patients enrolled in PANTHER or in Abi Race. Samples were batched and sera assessed contemporaneously. Median levels for each hormone were calculated combining both study populations and used as a cut point. Cox proportional hazard models were used to calculate the hazard ratio for rPFS associated with above or below median in the overall populations and stratified by race. Results: In the Abi Race study, baseline androgen levels did not associate with differences in rPFS for the group as a whole. In the PANTHER study, baseline levels of 11-OHT and 11-KT above the median were the only androgens significantly associated with longer rPFS for the entire group (Table). For both androgens, when stratified by androgen and race, Black men with baseline 11-OHT and 11-KT levels above the median had the best outcomes. (see Table). In the PANTHER study, in which treatment was stopped at two years, androgens were not predictive for overall survival. Conclusions: Elevated baseline serum levels of the adrenal androgens 11-OHT and 11-KT were associated with improved rPFS for patients treated with combination Apa and AA + P, particularly Black men. These results suggest the hypothesis that higher baseline 11-OHT and 11-KT may reflect a prostate cancer biology that is sensitive to combination ARPI. Larger prospective studies are needed to evaluate this hypothesis in mHSPC and mCRPC. Baseline 11-OHT and 11-KT levels, race and treatment outcome in PANTHER. 11-OHT 11-KT rPFS Cohort Level HR 95% CI Level HR 95% CI All pts > Med 1 > Med 1 All pts < Med 2.6 1.5, 4.7 < Med 2.0 1.1, 3.5 Black > Med 1 > Med 1 Black < Med 2.6 0.9, 7.0 < Med 2.31 0.9, 6.2 White > Med 2.3 0.9, 5.8 > Med 2.66 1.1, 6.7 White < Med 5.9 2.5, 14.3 < Med 4.27 1.8, 10.2