FDA Approves First Treatment for Nonmetastatic CRPC

February 16, 2018

The approval of the oral androgen-receptor inhibitor apalutamide (Erleada) is the first to be based on metastasis-free survival.

The US Food and Drug Administration (FDA) has approved the oral agent apalutamide (Erleada) for the treatment of nonmetastatic castration-resistant prostate cancer. The oral androgen-receptor inhibitor is the first FDA-approved treatment for patients with nonmetastatic castration-resistant disease and the first to be approved based on the endpoint of metastasis-free survival.

"The FDA evaluates a variety of methods that measure a drug’s effect, called endpoints, in the approval of oncology drugs. This approval is the first to use the endpoint of metastasis-free survival, measuring the length of time that tumors did not spread to other parts of the body or that death occurred after starting treatment,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a press release. “In the trial supporting approval, Erleada had a robust effect on this endpoint. This demonstrates the agency’s commitment to using novel endpoints to expedite important therapies to the American public."

The drug was approved based on the results of the phase III SPARTAN trial, in which 1,207 patients were randomly assigned 2:1 to treatment with apalutamide at 240 mg per day or placebo. All patients on the trial were treated with hormone therapy using either gonadotropin-releasing hormone analog therapy or surgical castration.  The primary endpoint was metastasis-free survival.

Median metastasis-free survival for patients assigned apalutamide was more than 2 years longer than for patients assigned to the placebo group (40.5 months vs 16.2 months; hazard ratio [HR] for metastasis or death, 0.28; 95% CI, 0.23–0.35; P < .001). In addition, time to symptomatic progression was significantly longer for patients assigned apalutamide compared with placebo (HR, 0.45; 95% CI, 0.32–0.63; P < .001).

Common side effects of apalutamide include fatigue, hypertension, rash, diarrhea, nausea, weight loss, arthralgia, falls, hot flush, decrease appetite, fractures, and peripheral edema.

“While there have been advances in the treatment of prostate cancer over the years, metastatic castration-resistant prostate cancer is still a lethal disease. These compelling results are the first to show that metastases can be delayed in these patients,” Eric Small, MD, FASCO, Professor of Medicine, and Chief of the Division of Hematology and Oncology at the University of California, San Francisco, and lead SPARTAN study investigator, said in a press release. “These data suggest that apalutamide could potentially be a new standard of care for patients with nonmetastatic castration-resistant prostate cancer.”

Results from SPARTAN were presented at the 2018 Genitourinary Cancers Symposium and published in The New England Journal of Medicine.