Predictive associations between serum dehydroepiandrosterone sulfate (DHEAS) and race among patients (pts) treated with apalutamide (apa), abiraterone acetate (AA) plus prednisone (P) in the PANTHER study.

PANTHER is a multicenter prospective trial of Black and White cohorts of metastatic castration resistant prostate cancer (mCRPC) patients (pts) treated with open label Apa and AA +P. We previously reported the 24-month radiographic progression-free survival (rPFS) for Black and White men were 61% (95% CI 49, 78) and 38% (95% CI 27, 54), while the 36-month overall survival (OS) rates were 68% (95% CI 55, 83) and 50% (95% CI 37, 66), respectively. In contrast, a similarly designed prospective study in mCRPC pts treated with AA + P (Abi Race) demonstrated no clear differences in rPFS or OS. We explored baseline hormonal levels associated with race in PANTHER and Abi Race, and their association with treatment outcomes. We measured levels of 12 steroid hormones using LC/MS-MS in available serum samples obtained at baseline and at 4 weeks of therapy from 161 of the 193 patients enrolled in PANTHER (n=86) and in Abi Race (n=75). Samples were batched and all 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 and OS associated with above or below median in the overall populations and stratified by race. Median baseline DHEAS was 49 mg/dl, with Black pts demonstrating a slightly higher median level (52 mg/dl; range 7-248) than White pts (42 mg/dl; 4-220). BaselineDHEAS levels below the median demonstrated a non-significant trend towards shorter outcomes in Abi Race: rPFS (HR 1.22, 95% CI 0.70, 2.15) and OS (HR 1.20; 95% CI 0.66, 2.18), and in PANTHER: rPFS (HR 1.54, 95% 0.87, 2.73) and OS (HR 1.14; 95% CI 0.67,1.95). When evaluated by race and DHEAS levels, patients in Abi Race demonstrated no clear association with outcomes. In contrast, Black patients with elevated DHEAS levels in PANTHER demonstrated the greatest rPFS and OS, with significant differences in HRs compared to White patients, ranging from 2.65 to 3.67 for rPFS and 2.20 to 2.43 for OS (see Table). Elevated baseline DHEAS levels may have positive predictive significance for rPFS and OS in Black men treated with combination Apa and AA + P compared to White men, but not when treated with AA + P alone. Larger prospective studies are needed. If confirmed, these results support the hypothesis that some Black men may disproportionately benefit from combined androgen signaling pathway inhibition. .

Duke Scholars

Author Andrew John Armstrong Medicine, Medical Oncology

Author Susan Halabi Biostatistics & Bioinformatics, Division of Biostatistics