Findings from the phase III placebo-controlled SPARTAN trial suggest that apalutamide is an effective treatment for men with nonmetastatic castration-resistant prostate cancer who are at high risk for developing metastatic disease and for whom no approved treatments exist. Men who received apalutamide had a 72% lower risk of metastasis or death than those who received placebo. These findings—which, according to the authors, may be relevant to about 100,000 men in the United States—will be presented by Small et al at the upcoming 2018 Genitourinary Cancers Symposium in San Francisco (Abstract 161).
“Until this trial, there have been no drugs proven to benefit men with nonmetastatic prostate cancer that has progressed despite standard hormonal therapy. These results show that apalutamide made a significant difference in prolonging the time before the development of metastasis,” said lead study author Eric J. Small, MD, FASCO, Professor of Medicine at the University of California, San Francisco.
There are no U.S. Food and Drug Administration–approved agents for the treatment of nonmetastatic castration-resistant prostate cancer, and some physicians advocate watchful waiting for these patients. However, men whose prostate-specific antigen (PSA) score is rapidly rising while on androgen-deprivation therapy (ADT) with a PSA doubling time of less than 8 to 10 months are at a significantly increased risk of developing metastases or death. This group represented the men enrolled in the SPARTAN study.
The SPARTAN study was conducted at 332 institutions worldwide and enrolled 1,207 men. Patients with nonmetastatic castration-resistant prostate cancer who had stopped responding to ADT and were at high risk of metastasis based on a PSA doubling time of 10 months or less were randomly assigned to receive apalutamide or placebo taken as daily tablets, added to ongoing ADT. At the time of development of metastases, patients were treated with standard second therapies at their physician’s discretion and had an option to receive on-study abiraterone acetate (Zytiga) and prednisone, a standard of care.
The median PSA doubling time at study entry was approximately 4.5 months in both the apalutamide and placebo groups. Apalutamide decreased the risk of metastasis and death by 72% compared with placebo, and significantly prolonged the median metastasis-free survival by 2 years (40.5 months in the apalutamide group vs 16.2 months in the placebo group).
At this interim analysis for overall survival, researchers also noted a trend favoring improved overall survival for men receiving apalutamide vs placebo, although the difference was not statistically significant. Following the analysis of metastasis-free survival, study treatment was unblinded in July 2017 following the recommendations of an Independent Data Monitoring Committee, and all patients were offered open-label apalutamide.
Apalutamide was well tolerated, with 10.7% of men discontinuing treatment due to adverse events compared with 6.3% of men receiving placebo. Quality-of-life scores were maintained in those men receiving apalutamide added to ADT.
“These data demonstrate that the use of apalutamide prior to the development of metastases clearly benefited patients whose prostate cancer no longer responded to conventional hormonal therapy,” said Dr. Small. ““It is exciting that there now exists such a well-tolerated agent for this group of high-risk patients for whom no approved therapies currently exist.”
The authors hope to identify those patients who benefited most from apalutamide by analyzing molecular and circulating markers from blood samples. They will also look in greater depth at patient-reported outcomes that evaluate the trial success or failure from a patient perspective.
“There is a population of men with prostate cancer who have no visible evidence of spread but who have a rise in their blood markers. These patients can have a poor prognosis, and until now, the optimal management of their cancer remained an enigma. These findings suggest there may finally be a treatment that holds real promise for extending their health and their lives,” said ASCO Expert Sumanta K. Pal, MD.
The SPARTAN study was funded by Aragon Pharmaceuticals, Inc, a wholly owned subsidiary of Johnson & Johnson.
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