Published: Aug. 16, 2012
Updated: Aug. 16, 2012
By Sarah Avery
Prostate Cancer Drug Q&A
A new oral hormone drug for advanced prostate cancer, enzalutamide, is expected to be approved by the U.S. Food and Drug Administration later this year after clinical trials at Duke Cancer Institute and elsewhere demonstrated promising results.
Duke’s Andrew Armstrong, M.D., was co-author of a report published Aug. 15, 2012, in the New England Journal of Medicine showing a 4.8-month improvement in median overall survival, to 18.4 months for patients taking the investigational once-daily pill, compared to 13.6 months for patients taking a placebo.
Armstrong , an associate professor of medicine, said the Duke Cancer Institute has one of the leading sites to enroll patients in the Phase III trial of enzalutamide. He offered these insights:
Q: Who were the patients enrolled in this drug study?
A: These were all men with hormone resistant, metastatic prostate cancer, which means their cancer progressed and spread after receiving hormonal therapy and first-line chemotherapy with docetaxel. Overall, the study enrolled a very large number of men, 1,199 at more than 150 centers in 15 countries, and Duke was one of the largest enrollment sites.
Q: What were some of the results that have generated such excitement among oncologists and patients?
A: This drug showed results that aren’t often seen in cancer studies. In addition to the nearly five-month improvement in overall survival, the drug dramatically reduced PSA levels in 54 percent of men, compared to 2 percent on placebo. It also extended the period that the cancer didn’t grow, to 8.3 months vs. 2.9 months. Quality of life scores also improved, along with other secondary measures, and the toxicity was quite similar to that of a placebo pill.
What is so exciting is that this agent is a hormonal therapy and worked in men who were thought to be resistant to all hormonal therapies. Thus, this treatment and others like it are changing how we think of prostate cancer.
Q: Were there any side effects?
A: There did appear to be a bit more fatigue, a slightly elevated risk of falls, more hot flashes and a small but noticeable seizure risk. Six patients out of 800 who received enzalutamide experienced a seizure, but some seizures had other potential explanations such as cancer spreading into the brain or other medications that may have contributed.
Q: When would you expect enzalutamide to be available?
A: The manufacturers (Medivation, Inc. and Astellas Pharma) submitted their application to the FDA in May, and we are hoping it will be approved before the end of the year, ideally this fall.
Q: Can patients get the drug now at Duke through any clinical trials?
We are actively pursuing trials in earlier pre-chemotherapy settings for men with advanced prostate cancer, including one that is slated to begin later this fall. It will involve patients with progressive non-metastatic or metastatic prostate cancer who have failed androgen deprivation therapy but have not yet received chemotherapy.
Q: This drug is one of several new therapies that have recently shown benefit for prostate cancer patients – it seems these are encouraging times for men with this disease.
A: There really have been some exciting developments. Abiraterone acetate (marketed as Zytiga) is a hormone treatment that was approved last year for men with advanced disease who had already undergone chemotherapy, and it had similarly exciting findings to enzalutamide. Cabazitaxel (marketed as Jevtana) and sipuleucel-T (marketed as Provenge) came on the market in 2010. Denosumab (Xgeva) has shown benefit in reducing pain and fractures due to prostate cancer in the bone. And there is a new radioisotope therapy (alpharadin, or radium-223) that seeks out bone metastases and has demonstrated improvement in survival and quality of life.
So it’s been a very good two years. However, we can do better, and efforts are ongoing at Duke and elsewhere to build upon this success.