A phase 3 trial designed to assess the addition of enzalutamide to androgen deprivation therapy for men with nonmetastatic castration-resistant prostate cancer met its primary endpoint of improved metastasis-free survival, according to the agents’ manufacturers.
Enzalutamide (Xtandi; Astellas, Medivation) is the first androgen receptor inhibitor to confer a statistically significant benefit in metastasis-free survival to this patient population in a randomized, controlled clinical trial.
Enzalutamide is approved in the United States for treatment of men with metastatic castration-resistant prostate cancer. Representatives of Astellas and Medivation — which Pfizer acquired last year — intend to discuss the data with regulatory authorities in hopes of expanding the label of enzalutamide to include men with nonmetastatic disease.
The randomized, phase 3, double-blind, placebo-controlled PROSPER trial included approximately 1,400 men with nonmetastatic castration-resistant prostate cancer that had progressed as determined by rising PSA level despite ADT. The men had no symptoms and no evidence of metastatic disease.
Researchers assigned men to ADT plus 160-mg once-daily enzalutamide, or ADT plus placebo. Metastasis-free survival served as the primary objective.
“We are delighted with the significant results seen in the PROSPER study, showing that Xtandi plus ADT delayed clinically detectable metastases compared to ADT alone in patients with nonmetastatic castration-resistant prostate cancer whose only sign of underlying disease was a rapidly rising PSA level,” Mace Rothenberg, MD, chief development officer for oncology with Pfizer Global Product Development, said in a press release. “Xtandi is already established as a standard of care for men with metastatic castration-resistant prostate cancer based on the results of prior studies, such as AFFIRM and PREVAIL, which demonstrated that Xtandi delayed disease progression and improved OS in men with clinically detectable metastatic disease.”
Preliminary analysis from the trial suggested a safety profile comparable to that observed with enzalutamide in previous studies.
The most common adverse reactions reported in enzalutamide-treated patients in two previous placebo-controlled trials included asthenia/fatigue, back pain, decreased appetite, constipation, arthralgia, diarrhea, hot flush, upper respiratory tract infection, peripheral edema, dyspnea, musculoskeletal pain, weight decreased, headache, hypertension, and dizziness/vertigo.
Detailed efficacy and safety results will be submitted for presentation at a medical meeting.
“We want to thank the patients, family members and clinicians who participated in the PROSPER trial and helped advance the scientific understanding of the potential role for Xtandi in this prevalent disease,” Steven Benner, MD, senior vice president and global therapeutic area head for oncology development at Astellas, said in the release.