Chicago, Illinois—The addition of abiraterone acetate to enzalutamide increased the number of adverse events and did not prolong survival in men with metastatic castration-resistant prostate cancer (mCRPC), according to recent research presented at the 2019 ASCO Annual Meeting.

“Androgen receptor (AR) signaling is an important growth mechanism in mCRPC, providing the rationale for treatment with AR axis inhibitors such as ENZ [enzalutamide] and AAP [abiraterone and prednisone],” explained Michael J. Morris, MD, Memorial Sloan Kettering Cancer Center, New York, and colleagues.

“Targeting AR with anti-androgens such as ENZ [enzalutamide] can result in compensatory autocrine and paracrine androgenic stimulation,” they added. 

To better understand how combination therapy with enzalutamide and abiraterone and prednisone impact patients with mCRPC compared with enzalutamide alone, Dr Morris et al enrolled 1311 men with progressive mCRPC into their study.

Between January 2014 and August 2016, the study participants were randomized in a 1:1 ratio to receive enzalutamide alone or in combination with abiraterone and prednisone. The primary end point of the study was overall survival (OS; ie, date of randomization to death or last follow-up), and a secondary end point was prostate-specific antigen (PSA) declining during therapy.

Changes in imaging and serum biomarkers (eg, androgens, angiokines, and circulating microRNA and RNA) were exploratory end points.

A total of 657 patients received enzalutamide alone and 654 received enzalutamide plus abiraterone and prednisone; 15.6% of patients were high-risk, 35.3% were intermediate-risk, and 48.1% were low-risk.

Findings shows that the median OS was 33.6 months (95% CI, 30.5-36.4) and 32.7 months (95% CI, 29.9-35.4) with enzalutamide and enzalutamide plus abiraterone and prednisone, respectively (2-sided P = .53). Dr Morris et al also noted that the 50% PSA decline rate was 80% versus 76.5% in each arm, respectively.

Adverse events grade 3-5 occurred in 55.6% of patients treated with enzalutamide alone and 68.8% of patients treated with the combination regimen; 5% and 12% of patients discontinued therapy due to adverse events, respectively, and 5% and 13% withdrew, respectively.

Ultimately, disease progression or death occurred in 57% and 48% of patients in the enzalutamide alone and combination arms, respectively.

“Addition of abiraterone acetate to enzalutamide did not prolong survival in men with mCRPC. The combination resulted in more AEs [adverse events] than enzalutamide alone,” Dr Morris and colleagues concluded.—Julie Gould

Morris MJ, Heller G, Bryce AH, et al. Alliance A031201: A phase III trial of enzalutamide (ENZ) versus enzalutamide, abiraterone, and prednisone (ENZ/AAP) for metastatic castration resistant prostate cancer (mCRPC). Presented at: the 2019 ASCO Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 5008.