FDA Accepts Label Revision for Prostate Cancer Drug

Astellas Pharma Inc and Pfizer Inc have announced that the FDA approved a supplemental New Drug Application for Xtandi (enzalutamide) capsules.

The approval will allow the companies to update the product labeling for the drug to include new clinical data from a phase 2 study, according to a press release. Findings from the TERRAIN study indicated that Xtandi increases radiographic progression-free survival in patients with metastatic castration-resistant prostate cancer compared with patients treated with bicalutamide.

Included in the study were 375 treatment-naïve patients randomized 1:1 to receive daily treatment with Xtandi or bicalutamide. The primary objective of the study was radiographic progression-free survival.

Serious grade 3 and 4 adverse reactions were seen in 38.8% of patients treated with Xtandi, including 2 patients experiencing a seizure. The most common adverse reactions included asthenic conditions, back pain, musculoskeletal pain, hot flush, hypertension, diarrhea, upper respiratory tract infection, and weight loss, according to the press release.

The results indicate that Xtandi reduces the risk of radiographic progression or death by 40% compared with bicalutamide, according to the study. Patients in the Xtandi group showed progression free survival of 19.5 months, compared with 13.4 months for those in the bicalutamide group (hazard ratio = 0.60 [0.43, 0.83]; 95% confidence interval).

“We are pleased with the FDA’s decision to update the XTANDI label with these data from the first and largest comparative trial that demonstrated safety and efficacy of enzalutamide compared to bicalutamide,” said Mohammad Hirmand, MD, interim chief medical officer at Medivation, Inc., which is now part of Pfizer. “We believe these data will help physicians better understand the differences between enzalutamide and bicalutamide for their patients living with metastatic CRPC.”

Each year, approximately 181,000 new cases of prostate cancer are diagnosed, and the American Cancer Society reports that 26,000 men will die from the disease. Patients with metastatic disease have only a 28% five-year survival rate, highlighting the need for more effective treatment options.

Xtandi is an androgen receptor blocker that has shown the ability to completely inhibit binding to androgen receptors, and also inhibits androgen receptor nuclear translocation and interaction with DNA, according to the press release. The companies warn that the medication is not indicated for use in women, and may cause fetal harm that can result in loss of pregnancy.

The FDA previously approved Xtandi for use in patients with metastatic castration-resistant prostate cancer. The European Medicines Agency issued a positive opinion that recommends the approval of the label for use in Europe.

“The addition of data from the TERRAIN trial continues to build the body of evidence that demonstrates the clinical impact XTANDI can have for patients living with metastatic CRPC,” said Steven Benner, MD, senior vice president, therapeutic area head for oncology development, Astellas. “Advances in scientific knowledge as seen through clinical trials like TERRAIN would not be possible without the participation of hundreds of patients, family members and clinical investigators, and we thank them for their valuable contributions.”