(ChemotherapyAdvisor) – Corticosteroid (CS) use during treatment with the androgen receptor inhibitor enzalutamide (ENZA) reduces overall survival (OS) and increases adverse event (AE) rates among men with metastatic castration-resistant prostate cancer (mCRPC) who previously underwent docetaxel therapy, according to an analysis of data from the randomized, placebo-controlled phase 3 AFFIRM study. The findings were presented at the 2013 Genitourinary Cancers Symposium in Orlando, FL.
“In this post-hoc analysis, on study CS use was associated with reduced OS and higher rates of grade 3 -4 AEs in mCRPC patients post-docetaxel,” reported lead author Howard I. Scher, MD, Chief of Genitourinary Oncology Service at the Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, New York, NY[NR1] .
Grade 3/4 AE rates were 63.3% among patients who took CS during the study compared with 34.4% in those patients who did not take CS, Dr. Scher’s team reported[NR2] .
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“While CS patients had worse outcomes, ENZA was consistently superior to placebo regardless of on-study CS use,” Dr. Scher and coauthors noted. ENZA was superior to placebo for OS, radiographic progression free survival, and time to PSA progression“regardless of CS use,” they reported[NR3] .
The mechanisms underlying the negative association between CS use and survival time for these patients remain unclear, the authors noted.
“The inferior outcomes in CS patients may be due to unmeasured confounders or the biologic properties of CS use itself,” they suggested[NR4] .
The AFFIRM trial had previously found that ENZA increased OS by 4.8 months (HR, 0.63; P<0.001) compared to placebo in men with mCRPC previously treated with docetaxel. But CS activate androgen receptors in preclinical models and a previously reported analysis of AFFIRM data had found CS use at baseline to be associated with inferior OS[NR5] .
The new analysis of AFFIRM data sought to evaluate whether or not the same was true of CS use during ENZA therapy. AFFIRM participants were randomized 2:1 to receive either ENZA (160 mg/d) or placebo, the authors reported. Participants were “allowed but not required” to take corticosteroids.
“On-study CS use was defined as oral CS user for 1 day or longer on study,” the authors reported. “On-study CS use was 48% in ENZA and 45% in placebo patients.”
The 2013 Genitourinary Cancers Symposium is co-sponsored by the American Gastroenterological Association (AGA) Institute, the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO) and the Society of Urologic Oncology (SUO).
Clinical trial information: NCT00974311.
Abstract [http://gucasym.asco.org/content/107227-134]
