(UroToday.com) The treatment landscape in advanced prostate cancer has rapidly evolved. In particular, agents with demonstrated survival benefits later in the natural history of prostate cancer have been used earlier in the disease process. In the context of metastatic castration resistant prostate cancer (mCRPC), docetaxel was the first agent to demonstrate a survival benefit when combined with conventional androgen deprivation therapy (ADT). Subsequently, docetaxel demonstrated benefit in metastatic hormone-sensitive prostate cancer (mHSPC), also referred to as metastatic castration-sensitive prostate cancer. Following this, a number of other treatment approaches have been assessed and are now clinically used including androgen receptor targeting agents, such as abiraterone acetate. Due to its mechanism of action, abiraterone acetate requires co-administration with an oral corticosteroid. Previous randomized control trials (RCTs) have shown increased cardiac risk with abiraterone acetate + androgen deprivation therapy (ADT).
In a podium presentation at the American Urologic Association Virtual Annual Meeting, Dr. Hall and colleagues examined the available evidence regarding the cardiotoxicity of abiraterone acetate via meta-analysis, focusing on mechanistically related side-effects and differences based on disease indication and trial design.
To do so, they performed a systematic review and meta-analysis of phase II and III RTCs of abiraterone acetate +ADT vs ADT for patients with prostate cancer published as of 8/11/2020. Their primary outcomes were hypokalemia and fluid retention, and secondary outcomes were cardiac disorders and hypertension. They performed meta-analysis comparing intervention (including abiraterone acetate) and control, stratifying according to disease state (HSPC, pre-chemo mCRPC, vs post-chemo mCRPC) and trial design (steroids in the control arm).
Their systematic review identified 2739 search results, among which 6 studies of 5,901 patients with HSPC (including mHSPC and advanced localized disease) or mCRPC were included. In the intervention arm, patients received abiraterone acetate 1000mg, ADT, and steroid, and controls received ADT, placebo, +/- steroid.
Patients receiving abiraterone acetate were more likely to experience hypokalemia (17.3% vs 6.0%, p <0.001), fluid retention (24.1% vs 17.6%, p <0.001), hypertension (25.3% vs 15.1%, p <0.001), and cardiac events (25.4% vs 15.9%, p=0.002) than controls. The apparent effect of abiraterone acetate on these outcomes was significantly modified on the basis of whether patients in the control arm received steroid with placebo (hypokalemia: p <0.001, hypertension: p=0.01, and cardiac disorders: p <0.001) and on the basis of disease state/indication (hypokalemia: p <0.001, hypertension: p=0.03, and cardiac disorders: p=0.01).
The authors conclude that both disease indication (mCSPC vs mCRPC) and nuances of study design (including whether steroids were administered to patients in the control arm), meaningfully affect the magnitude of apparent attributable mechanistic toxicities of abiraterone acetate. These hypothesis-generating data may be helpful in understanding abiraterone acetate toxicity and offering individualized counseling.
Presented by: Mary Hall, MD, Urology Resident, Vanderbilt University Medical Center
Written by: Christopher J.D. Wallis, University of Toronto, Twitter: @WallisCJD during the 2021 American Urological Association, (AUA) Annual Meeting, Fri, Sep 10, 2021 – Mon, Sep 13, 2021.