Enzalutamide With Standard Therapy in Metastatic Prostate Cancer

[Balsam01]

TAKE-HOME MESSAGE

•It is not known whether adding enzalutamide to testosterone suppression, with or without early docetaxel, will improve survival in men with metastatic, hormone-sensitive prostate cancer. The authors performed a randomized trial wherein 1125 men were assigned to receive testosterone suppression plus either open-label enzalutamide or a standard nonsteroidal antiandrogen therapy. The primary endpoint was overall survival. With a median follow-up of 34 months, overall survival was 80% in the enzalutamide group and 72% (based on 130 events) in the standard-care group. Similar benefits were seen in PSA and clinical progression with enzalutamide over standard therapy. The enzalutamide group had more frequent treatment discontinuation due to adverse events than the standard-care group. Seizures occurred in 7 patients in the enzalutamide group (1%) and in no patients in the standard-care group.

•The authors concluded that enzalutamide in combination with androgen-deprivation therapy (ADT) is superior to ADT plus standard antiandrogen therapy and leads to an improvement in overall survival. Docetaxel-pretreated patients have a higher incidence of adverse events. Further data will need to clarify the optimal sequence and utility of chemotherapy and ADT.

– Gautam Jayram, MD

abstract

This abstract is available on the publisher's site.

BACKGROUND

Enzalutamide, an androgen-receptor inhibitor, has been associated with improved overall survival in men with castration-resistant prostate cancer. It is not known whether adding enzalutamide to testosterone suppression, with or without early docetaxel, will improve survival in men with metastatic, hormone-sensitive prostate cancer.

METHODS

In this open-label, randomized, phase 3 trial, we assigned patients to receive testosterone suppression plus either open-label enzalutamide or a standard nonsteroidal antiandrogen therapy (standard-care group). The primary end point was overall survival. Secondary end points included progression-free survival as determined by the prostate-specific antigen (PSA) level, clinical progression-free survival, and adverse events.

RESULTS

A total of 1125 men underwent randomization; the median follow-up was 34 months. There were 102 deaths in the enzalutamide group and 143 deaths in the standard-care group (hazard ratio, 0.67; 95% confidence interval [CI], 0.52 to 0.86; P=0.002). Kaplan–Meier estimates of overall survival at 3 years were 80% (based on 94 events) in the enzalutamide group and 72% (based on 130 events) in the standard-care group. Better results with enzalutamide were also seen in PSA progression-free survival (174 and 333 events, respectively; hazard ratio, 0.39; P<0.001) and in clinical progression-free survival (167 and 320 events, respectively; hazard ratio, 0.40; P<0.001). Treatment discontinuation due to adverse events was more frequent in the enzalutamide group than in the standard-care group (33 events and 14 events, respectively), higher in the docetaxel pretreated group.

CONCLUSIONS

Enzalutamide was associated with significantly longer progression-free and overall survival than standard care in men with metastatic, hormone-sensitive prostate cancer receiving testosterone suppression. The enzalutamide group had a higher incidence of seizures and other toxic effects, especially among those treated with early docetaxel.

The New England Journal of Medicine.

Enzalutamide With Standard First-Line Therapy in Metastatic Prostate Cancer.

N. Engl. J. Med 2019 Jun 02;[EPub Ahead of Print], ID Davis, AJ Martin, MR Stockler, et al

[pjoshea13]

"testosterone suppression plus either open-label enzalutamide or a standard nonsteroidal antiandrogen therapy"

Essentially comparing Xtandi with "bicalutamide, nilutamide, or flutamide"

[1]

"All the patients received testosterone suppression, plus the addition of docetaxel when appropriate."

"The effect of enzalutamide on overall survival appeared to be smaller in the subgroup with early docetaxel treatment."

-Patrick

[1] nejm.org/doi/full/10.1056/N...