Enzalutamide may benefit some men with metastatic castration-resistant prostate cancer (mCRPC) whose disease progresses while on treatment with abiraterone plus prednisone, according to a new study.

In a prospective, open-label, single-arm, multicenter study, Johann S. De Bono, MD, of the Institute of Cancer Research in London, and colleagues examined the outcomes of 214 mCRPC patients treated with enzalutamide after their disease progressed while on abiraterone plus prednisone for at least 24 weeks. The primary study outcome was radiographic progression-free survival (rPFS).

The median duration of enzalutamide treatment was 5.7 months for the overall study population, with 30% of patients remaining on treatment at 9 months, the investigators reported online ahead of print in European Urology. The median duration of enzalutamide treatment was similar for patients who received prior chemotherapy and those who did not (5.5 vs 5.9 months). The median rPFS was 8.1 months and median time to PSA progression was 5.7 months.

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Radiographic progression occurred in 101 (72%) of the 141 patients who experienced disease progression. Forty deaths occurs before experiencing radiographic progression.

Abiraterone and enzalutamide are novel androgen receptor (AR)-targeted agents, and retrospective analyses suggest some cross-resistance between these drugs when used sequentially, the authors noted, adding that findings from robust, prospective studies have not yet been reported.

“Currently, there is no expert consensus on the use of second-line treatment with enzalutamide or abiraterone in symptomatic men who develop resistance after first-line abiraterone or enzalutamide, respectively, due in part to the absence of prospective clinical data in these settings,” the authors wrote.

The prospective data from their study demonstrate the antitumor activity of enzalutamide in patients who progressed following 24 weeks or more of abiraterone treatment and support the use of enzalutamide in some patients in the post-abiraterone setting, they stated.

Overall, the authors noted, a better understanding of the biology of abiraterone and enzalutamide resistance is key to optimizing use of these agents.

In an accompanying editorial, Kazutaka Saito, MD, and Yasuhisa Fujii, MD, of Tokyo Medical and Dental University in Japan, said the new study provides further important findings on the antitumor activity of enzalutamide as a second-line AR-targeted agent in a prospective, multicenter study. “A next step would be to identify predictive variables for appropriate patient selection for a trial of second-line enzalutamide following abiraterone in a suitable disease setting,” they wrote.


De Bono JS, Chowdhury S, Feyerabend S, et al. Antitumour activity and safety of enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with abiraterone acetate plus prednisone for ≥24 weeks in Europe. Eur Urol. 2017; published online ahead of print.


Saito K, Fujii Y. Antitumor activity and safety of enzalutamide after abiraterone acetate: Seeking the optimal treatment sequence for castration-resistant prostate cancer patients. Eur Urol 2017; published online ahead of print.