While abiraterone acetate (AA) has demonstrated survival benefit in advanced prostate cancer (APC), meaningful cardiotoxicity is observed. It is unclear whether the magnitude differs based on disease indication and concurrent steroid administration.
We performed a systematic review and meta-analysis of phase II/III RCTs of AA in APC published as of August 11, 2020. Primary outcomes examined were all- and high-grade (grade ≥ 3) hypokalemia and fluid retention, and secondary outcomes included hypertension and cardiac events. We performed random effects meta-analysis comparing intervention (AA + steroid) and control (placebo ± steroid), stratified by treatment indication and whether patients received steroids.
Among 2,739 abstracts, we included 6 relevant studies encompassing 5901 patients. Hypokalemia and fluid retention were observed more frequently among patients receiving AA (odds ratio [OR] 3.10 [95% CI 1.69-5.67] and 1.41 [95% CI 1.19-1.66]). This was modified by whether patients in the control received steroids: trials where control patients did not demonstrated a larger association between AA and hypokalemia (OR 6.88 [95% CI 1.48-2.36] versus OR 1.86 [95% CI 4.97-9.54], P < .0001) and hypertension (OR 2.53 [95% CI 1.91-3.36] vs. OR 1.55 [95% CI 1.17-2.04], P = .1) than those where steroids were administered. We observed heterogeneity due to indication: there were greater effects on hypokalemia (P < 0001), hypertension (P = .03), and cardiac disorders (P = .01) among patients treated for mHSPC than mCRPC.
The magnitude of cardiotoxicity with AA differs based on trial design and disease indication. These data are valuable in treatment decisions and highlight utilization of appropriate data for counseling.
Clinical genitourinary cancer. 2023 Apr 23 [Epub ahead of print]
Mary E Hall, Whitney J Padgett, Zachary Klaassen, Diana E Magee, Amy N Luckenbaugh, Aaron A Laviana, Raj Satkunasivam, Kerry Schaffer, Christopher J D Wallis
Department of Urology, Vanderbilt University Medical Center, Nashville, TN. Electronic address: ., Department of Urology, Vanderbilt University Medical Center, Nashville, TN., Division of Urology, Medical College of Georgia at Augusta University, Augusta, GA; Georgia Cancer Center, Augusta, GA., Division of Urologic Oncology, Department of Surgical Oncology, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA., Department of Surgery and Perioperative Care, University of Texas at Austin, Austin, TX., Department of Urology, Houston Methodist Hospital, Houston, TX; Center for Outcomes Research, Houston Methodist Hospital, Houston, TX., Department of Medical Oncology, Vanderbilt University Medical Center, Nashville, TN; Vanderbilt Ingram Cancer Center, Nashville. TN., Department of Urology, Vanderbilt University Medical Center, Nashville, TN; Division of Urology, Department of Surgery, University of Toronto, Toronto, ON, Canada; Division of Urology, Department of Surgery, Mount Sinai Hospital, Toronto, ON, Canada.