The US Food and Drug Administration (FDA) today approved apalutamide (Erleada, Janssen) for the treatment of patients with nonmetastatic prostate cancer who are at high risk for disease spread because treatment with hormone therapy is not effective and thus their disease is castration resistant.
This is the first FDA-approved treatment for nonmetastatic, castration-resistant prostate cancer. It is also the first time the FDA used metastasis-free survival (MFS) as the primary endpoint in its decision making.
"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," said Richard Pazdur, MD, acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, in a press statement.
Apalutamide is an orally administered androgen-receptor inhibitor.
The FDA based its new approval on safety and efficacy data from the phase 3 SPARTAN (Selective Prostate Androgen Receptor Targeting With ARN-509) trial. Investigators randomly assigned 806 men to receive treatment with apalutamide (240 mg per day) and 401 to receive placebo; all participants also received hormone therapy, either gonadotropin-releasing hormone analogue therapy or surgical castration.
All of the men had also undergone previous definitive treatment, either surgery or radiotherapy, for prostate cancer, but their PSA scores doubled within 10 months or less following treatment, despite hormone therapy.
Median MFS, which was the primary endpoint, was 40.5 months in the apalutamide group as compared with 16.2 months in the placebo group (P < .001). That translated into a 72% reduction in the relative risk for metastasis or death with the new drug (hazard ratio, 0.28; 95% confidence interval [CI], 0.23 - 0.35).
In addition, the results with apalutamide were superior for all secondary endpoints compared to placebo, including time to metastasis, progression-free survival, and time to symptomatic progression; all were significantly longer with apalutamide (P < .001 for all comparisons).
Median follow-up in the study was 20.3 months.
The findings were published in the New England Journal of Medicine and were presented last week at the Genitourinary Cancers Symposium (GUCS) 2018, as reported by Medscape Medical News.
"New Standard of Care"
"These data suggest that apalutamide should be considered as a new standard of care for men with high-risk nonmetastatic castrate-resistant prostate cancer," said lead study author Eric J. Small, MD, professor of medicine at the University of California, San Francisco, last week during a GUCS presscast.
In the trial, the rate of discontinuation due to adverse events was 10.6% in the apalutamide group and 7.0% in the placebo group. Three adverse events occurred more commonly with apalutamide than with placebo: rash (23.8% vs 5.5%), hypothyroidism (8.1% vs 2.0%), and fracture (11.7% vs. 6.5%).
Mean baseline health-related quality-of-life scores were maintained in both study groups. There was "no decrement in quality of life on apalutamide," Small said. There was also no difference in serious adverse events between the two groups.
In the past, no standard therapy was available for men with nonmetastatic, castration-resistant prostate cancer; patients were typically managed with surveillance.
Last week, an expert commented on the recently presented SPARTAN and PROSPER trials, both of which were conducted in this population but employed different androgen-receptor inhibitors.
"These trials are addressing a great clinical need for these patients, who currently generally only receive observation," said Alexander Kutikov, MD, chief of urologic oncology at Fox Chase Cancer Center in Philadelphia, Pennsylvania, who was not involved in the research.
"The reported results will undoubtedly disrupt the treatment paradigms for these patients, delay the time to metastatic disease, and, ultimately, hopefully prove to extend survival," he told Medscape Medical News.
According to the National Cancer Institute, approximately 10% to 20% of early-stage prostate cancers are castration resistant, and up to 16% of these patients show no evidence of metastasis at the time of that diagnosis.
However, the number of patients with nonmetastatic castration-resistant prostate cancer may decrease in the future, according to an expert.
That's because newer, improved imaging modalities are detecting metastatic spread earlier than the current standards of CT and conventional bone scanning, which were used in the SPARTAN trial, Sumanta K. Pal, MD, urologic oncologist at City of Hope in Duarte, California, said during the presscast.
In short, newer imaging technologies may make it possible to identify some cases of metastatic disease earlier and thus allow men to receive therapies already approved for such cancers.
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Cite this: FDA Approves Apalutamide for Nonmetastatic Prostate Cancer - Medscape - Feb 14, 2018.