Prostate Cancer Drug Fails in Clinical Trial

Pfizer and Astellas Pharma recently announced negative results from a phase 4 clinical trial of Xtandi (enzalutamide) capsules in patients with prostate cancer.

The companies revealed that the PLATO study did not meet its primary endpoint of improved progression-free survival (PFS) in patients with metastatic castration-resistant prostate cancer.

The clinical trial evaluated the safety and efficacy of Xtandi plus abiraterone acetate and prednisone compared with placebo plus abiraterone acetate and prednisone monotherapy, according to a press release from Pfizer.

There were 509 chemotherapy-naïve patients included in the trial who received Xtandi during the first period of the study. These patients received 160-mg of Xtandi in combination with 1000-mg of abiraterone and 5-mg of prednisone.

Once their cancer progressed, patients were randomized to receive 1 of the combination treatment options. Investigators defined PFS as radiographic progression, unequivocal clinical progression, or death, according to Pfizer.

“While the PLATO trial did not meet its primary endpoint, it is critical that we continue to focus on addressing the unmet needs of men with metastatic CRPC, who have a poor prognosis despite treatment advances,” said Mohammad Hirmand, MD, interim chief medical officer at Medivation, Inc., which is now part of Pfizer. “We will continue to analyze these data to better understand the results with the goal of further helping these patients.”

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.

Common adverse events seen in placebo-controlled patients included fatigue, back pain, diminished appetite, constipation, arthralgia, diarrhea, hot flush, upper respiratory tract infection, peripheral edema, dyspnea, musculoskeletal pain, weight loss, headache, hypertension, and vertigo, Pfizer reported.

Currently, Xtandi is approved for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC). Pfizer reported that the drug received this approval based on clinical results that demonstrate a significant increase in overall survival compared with placebo.

The companies recently received approval from the FDA to update product labeling for Xtandi to include results from the phase 2 TERRAIN study, which showed the drug can improve radiographic progression-free survival in these patients.

“Xtandi continues to remain an important treatment option for men with metastatic CRPC and their physicians. We are committed to continuing to explore the clinical potential of Xtandi across the disease continuum,” said Steven Benner, MD, senior vice president, therapeutic area head for oncology development at Astellas.