February 15, 2018—Yesterday, the U.S. Food and Drug Administration (FDA) approved the use of apalutamide, an oral androgen-receptor inhibitor, for the treatment of patients with prostate cancer that continues to grow following or during treatment with hormone therapy, but has not spread to other sites. This is the first approval for castration-resistant, nonmetastatic prostate cancer. This approval determination also marks the first use of metastasis-free survival (MFS) as a primary endpoint.

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,” said 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 in a press release. “In the trial supporting approval, [apalutamide] 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.

Approval of apalutamide was based on results from the multicenter, double-blind, phase III SPARTAN trial (NCT01946204) which randomizing 1,207 patients with nonmetastatic castration-resistant prostate cancer to receive androgen deprivation therapy in combination with 240 mg apalutamide, once daily, or placebo.

MFS was defined as the time from randomization to first evidence of distant metastasis by imaging, or death due to any cause. In results recently published in The New England Journal of Medicine, a median MFS of 40.5 months was reported for patients receiving apalutamide compared with 16.2 months for patients receiving placebo. Patients receiving apalutamide had a 72% reduced risk of metastasis or death.

Secondary endpoints from this trial included time to metastasis, progression-free survival, and time to symptomatic progression. All secondary endpoints were longer for patients receiving apalutamide.

Adverse events leading to discontinuation occurred in 10.7% of patients receiving apalutamide and 6.3% of patients in the control arm. Adverse events including rash, hypothyroidism, and fractures occurred at a higher rate for patients receiving apalutamide.

The FDA has approved apalutamide at a dose of 240 mg, once daily. Full prescribing information can be found here.

Jonathan A. Bell
Published Online: Thursday, February 15, 2018