Newswise — CHICAGO — Patients with castration-resistant prostate cancer treated with the androgen inhibitor abiraterone and who had high baseline hormone levels had longer overall survival compared with patients with low hormone levels, according to data presented at the AACR Annual Meeting 2012, held here March 31 - April 4.
If confirmed, these data mean that levels of hormones, specifically adrenal androgens, may provide physicians with another way to predict the efficacy of therapy in patients with metastatic, castration-resistant prostate cancer, according to Charles J. Ryan, M.D., associate professor of clinical medicine and urology at University of California-San Francisco Helen Diller Family Comprehensive Cancer Center in San Francisco, Calif.
“We have identified that patients who have higher levels of androgen compared with those with lower levels have a better prognosis overall and a better prognosis when receiving abiraterone than patients with lower levels of androgens,” said Ryan. “Patients with low hormone levels seem to have a worse prognosis overall; however, they still benefitted significantly from receiving abiraterone as opposed to receiving placebo.”
In the past, this form of prostate cancer was referred to as hormone-refractory prostate cancer. However, this term is no longer used because, in recent years, researchers have discovered that certain drugs, like abiraterone, which are essentially hormone therapies, improve outcomes and survival rates.
In this prospective substudy, Ryan and colleagues evaluated data from a randomized phase III trial that compared abiraterone to placebo and led to the approval of abiraterone. They categorized patients according to high levels or low levels of hormones.
The results indicated that higher baseline hormone levels were associated with significantly higher overall survival in patients regardless of initial treatment compared with low baseline levels. Patients assigned to placebo and who had high hormone levels had nearly 50 percent improvement in survival compared with those assigned to placebo and who had low hormone levels. In addition, abiraterone was associated with longer overall survival compared with treatment with placebo in patients with high and low levels of baseline hormones.
Patients assigned to abiraterone who had high baseline levels of hormones had almost twice the overall survival compared with those with low levels of hormones assigned to placebo.
“We used to think that it was not necessary to measure hormone levels once they were below normal — that was in part due to the fact that we were using insensitive assays,” Ryan said. “However, now we know that they have prognostic and predictive significance and that physicians treating these patients should think about conducting hormone tests.”
According to Ryan, more work is required to determine how these data will inform the standard-of-care management of patients with prostate cancer; however, it is likely that these data will affect the design of future clinical trials.
The study was sponsored by Cougar Biotechnology, which is owned by Johnson & Johnson.
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Presenter: Charles J. Ryan, M.D.
Abstract Number: LB-434
Title: Baseline serum adrenal androgens are prognostic and predictive of overall survival (OS) in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC): Results of the COU-AA-301 phase 3 randomized trial.
Author Block: Charles Ryan1, Jinhui Li2, Thian Kheoh3, Howard I. Scher4, Arturo Molina3. 1University of California-San Francisco, San Francisco, CA; 2Johnson & Johnson Pharmaceutical Research & Development, Raritan, NJ; 3Ortho Biotech Oncology Research & Development (Unit of Cougar Biotechnology), Los Angeles, CA; 4Memorial Sloan Kettering Cancer Center, New York, NY.
Objective: In COU-AA-301 the androgen biosynthesis inhibitor abiraterone acetate (AA) significantly increased OS vs placebo (PL) in mCRPC post-docetaxel (HR=0.74; Scher, ASCO 2011). The objective of the current study was to determine the effect of baseline levels of adrenal androgens (testosterone [T], androstenedione [A4], and dehydroepiandrostenedione [DHEA]) on OS in COU-AA-301.
Methods: COU-AA-301 is a randomized double blind study of AA (1000 mg QD + prednisone [P] 5 mg po BID) vs PL + P. In this post hoc exploratory analysis, the effect of baseline serum androgen levels (T, A4, DHEA) on OS was determined by univariate and multivariate analyses using the Cox proportional hazards regression model. Cut offs for high hormone (HH; above median) and low hormone (LL; below median) levels were used. Pts were stratified by ECOG PS (0-1 vs 2), pain (pain 4-10 [present] vs pain 0-3 [absent]), 1 vs 2 prior chemotherapy regimens, and type of progression (PSA only vs radiographic).
Results: Higher baseline serum androgens (T, A4, and DHEA) were associated with significantly improved OS, in either univariate or multivariate analysis, adjusting for treatment, other androgens, and other lab parameters (ie, LDH, HGB, ALKP, PSA; all p<0.0001). OS was significantly longer in HH group vs LH group in both AA + P and PL + P arms for T, A4, and DHEA (Table); the longer OS observed with AA + P vs PL + P was observed in both HH and LH groups for T, A4, and DHEA.
Conclusions: In study COU-AA-301, baseline adrenal androgens were both prognostic and predictive of OS in patients with mCRPC. Pts treated with P alone had longer OS in the HH group vs LH group, suggesting P modulation of the adrenal axis. AA was beneficial in both HH and LH groups, but the effect appeared more pronounced in the HH group. Additional work is underway to further understand the relationship between serum and intratumoral androgens and outcomes.