Pfizer and Astellas Pharma announced that a Phase 4 clinical trial, investigating longer-term use of Xtandi (enzalutamide) as a combination treatment for patients with metastatic castration-resistant prostate cancer (mCRPC), did not reach its primary goal of improved progression-free survival. The trial is concluding but data will continue to be evaluated, the companies said.
Top-line results failed to show that continued treatment with Xtandi, in combination with the chemotherapy drugs Zytiga (abiraterone acetate) and prednisone, led to better progression-free survival in chemotherapy-naive mCRPC patients whose PSA levels had progressed despite previous Xtandi therapy.
“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,” Mohammad Hirmand, MD, chief medical officer at Medivation, a Pfizer company, said in a news release. “We will continue to analyze these data to better understand the results with the goal of further helping these patients.”
Xtandi is an oral, once-daily androgen receptor inhibitor that blocks, using three different steps, male hormones from signaling within tumor cells to prevent their growth. The U.S. Food and Drug Administration (FDA) approved Xtandi as a treatment for mCRPC patients in 2012, based on results from previous clinical trials showing a significant overall survival benefit with this drug.
The Phase 4 PLATO trial (NCT01995513) is a global, double-blind, placebo-controlled study, designed to assess the safety and efficacy of continued treatment with Xtandi plus Zytiga and prednisone following confirmed PSA progression.
The study enrolled 509 patients with mCRPC who had never received chemotherapy treatment before, and was divided in two parts. In part one, patients received Xtandi (160mg/day) until an increase in their PSA levels was confirmed.
In the second part, patients were randomly assigned to either continue Xtandi treatment, now combined with Zytiga (1,000 mg/day orally) and prednisone (5 mg administered orally twice daily), or treatment with only Zytiga and prednisone. Its primary goal was progression-free survival, defined by either radiographic progression, unequivocal clinical progression, or death.
“XTANDI continues to remain an important treatment option for men with metastatic CRPC and their physicians,” said Steven Benner, MD, senior vice president of Astellas. “We are committed to continuing to explore the clinical potential of XTANDI across the disease continuum.”