CHICAGO — Adding enzalutamide to abiraterone acetate and leuprolide acetate does not appear to be effective for the treatment of localized high-risk prostate cancer, a study presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting indicates.1

Although abiraterone acetate combined with medical castration increases cytoreduction in localized high-risk prostate cancer, persistent cancer is often observed. Therefore, researchers examine whether adding enzalutamide to that combination improves outcomes.

“We hypothesized that enzalutamide combined with abiraterone and acetate and leuprolide will achieve greater cytoreduction than abiraterone and leuprolide in castration-naïve localized high-risk prostate cancers,” said lead investigator Eleni Efstathiou, MD, PhD, associate professor of genitourinary medical oncology at The University of Texas MD Anderson Cancer Center in Houston.

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Investigators enrolled 65 patients with clinical stage T1c/T2 disease with biopsy Gleason score ≥8  or ≥T2b disease with a Gleason score ≥7 and a PSA >10 ng/mL. Patients were randomly assigned 2:1 to receive 24 weeks of neoadjuvant abiraterone acetate 1000 mg orally daily plus prednisone 5 mg orally daily and leuprolide acetate with or without enzalutamide 150 mg orally daily. All patients then underwent prostatectomy.

Pathologic downstaging (≤pT2N0) occurred in 30% of enzalutamide-treated patients compared with 52% of those who did not receive enzalutamide (P=.08), including 1 pathologic complete response in each arm, according to the data.

In terms of safety, grade 3 hypertension was more frequently reported with enzalutamide (44% vs 12%). Dose-limiting toxicities occurred in 6 patients in the enzalutamide arm and in 2 patients who did not receive enzalutamide.

“Enzalutamide plus abiraterone, leuprolide, and 5 mg of prednisone daily can be given safely for 6 months in men with localized high-risk prostate cancer prior to prostatectomy,” Dr Efstathiou noted.

Biomarker analyses further demonstrated that stage ≤pT2N0 was associated with lower Ki67 (P=.006) and increased expression of androgen receptor signaling components AR-N (P=.05) and PTEN (P=.01). Researchers also observed ARV7 presence more frequently in enzalutamide-treated tumors.

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“As a cautionary statement, taken together our findings point to a clinically relevant heterogeneity in hormone-naïve high-risk prostate cancers; however, the observations are limited by small study size and must be duplicated,” Dr Efstathiou concluded.


  1. Efstathiou E, Davis JW, Titus MA, et al. Neoadjuvant enzalutamide (ENZA) and abiraterone acetate (AA) plus leuprolide acetate (LHRHa) versus AA+ LHRHa in localized high-risk prostate cancer (LHRPC). J Clin Oncol. 2016; 34 (suppl; abstr 5002).