Recent Drug Approvals

Medscape Medical News > Oncology
Enzalutamide First-Line in Prostate Cancer: Trial Stopped
Zosia Chustecka
October 22, 2013
Editors’ Recommendations

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Drug & Reference Information

• Neoadjuvant Androgen Deprivation Therapy in Prostate Cancer
• Imaging in Prostate Carcinoma
• External Beam Radiotherapy in Prostate Cancer

The road ahead for first-line use in prostate cancer seems clear now for enzalutamide (Xtandi, Medivation/Astellas), after a pivotal phase 3 trial exploring this use of the drug was stopped early because of benefit.
After an interim analysis showed significantly better overall survival with enzalutamide compared with placebo, the Independent Data Monitoring Committee recommended that the trial be stopped, and that patients who were receiving placebo should be offered the active drug.
Enzalutamide is already approved for use in prostate cancer, but its current indication is for second-line therapy in men with metastatic castration-resistant prostate cancer who had previously received docetaxel. This indication was approved by the US Food and Drug Administration in August 2012, and was recently approved in the European Union. In addition, last week in the United Kingdom, the National Institute for Clinical Excellence announced that this use of enzalutamide in prostate cancer would be covered by the National Health Service.
The approval of enzalutamide for second-line use was based on results from the AFFIRM study, which showed a survival benefit in men with postdocetaxel prostate cancer, reducing the risk for death by 37% relative to placebo, extending survival by more than 4 months. At the time, enzalutamide, a first-in-class androgen-receptor inhibitor, was hailed by experts as a “game changer” in the treatment of prostate cancer.
New Results for First-Line Use
The new results for first-line use come from the PREVAIL trial, conducted in 1715 men with metastatic prostate cancer that had progressed, despite androgen-deprivation therapy, and who have not yet received chemotherapy. Patients were randomized to receive either enzalutamide (160 mg orally once daily) or placebo.
The manufacturers released top-line results from the study in a press release. The companies said that the results will be presented at an upcoming medical conference. The companies also said that they will talk to regulatory authorities about these data in early 2014.
The results show that patients treated with enzalutamide had significantly longer overall survival, showing a 30% reduction in risk for death compared with placebo (P < .0001), according to the companies.
At the time of the interim analysis, 72% of patients in the enzalutamide group and 65% in the placebo group were still alive, and the calculated point estimate for median overall survival was 32.4 months (95% confidence interval [CI], 31.5 months – upper limit not yet reached) for enzalutamide versus 30.2 months (95% CI, 28.0 months – upper limit not yet reached) for patients receiving placebo.
Enzalutamide also showed a significantly improved radiographic progression-free survival, showing an 81% reduction in risk for radiographic progression or death compared with placebo.
The median radiographic progression-free survival was not yet reached (95% CI, 13.8 months – upper limit not yet reached) in the enzalutamide group and was 3.9 months (95% CI, 3.7 – 5.4) in the placebo group.
Two patients were reported by investigators to have had a seizure event.
“To my knowledge, the benefits in overall survival and radiographic progression-free survival reported in today’s PREVAIL trial results are unprecedented in this patient population,” said Tomasz M. Beer, MD, FACP, professor of medicine and deputy director of the Knight Cancer Institute at Oregon Health & Science University in Portland, and the coprincipal investigator of the PREVAIL study.