Apalutamide significantly improved median metastasis-free survival by 2 years in men with nonmetastatic castrate-resistant prostate cancer (nmCRPC), according to study results presented by Eric Jay Small, MD, MD, FASCO, chief of the division of hematology and oncology in the department of medicine at the University of California, San Francisco (UCSF), deputy director of the UCSF Helen Diller Family Comprehensive Cancer Center, and professor in residence in the Department of Medicine and Department of Urology, at the 2018 Genitourinary Cancers Symposium.
Apalutamide significantly improved median metastasis-free survival (MFS) by 2 years in men with nonmetastatic castrate-resistant prostate cancer (nmCRPC), according to study results presented by Eric Jay Small, MD, MD, FASCO, chief of the division of hematology and oncology in the department of medicine at the University of California, San Francisco (UCSF), deputy director of the UCSF Helen Diller Family Comprehensive Cancer Center, and professor in residence in the Department of Medicine and Department of Urology, at the 2018 Genitourinary Cancers Symposium.
nmCRPC is a uniformly fatal disease that can develop either from metastatic hormone sensitive prostate cancer or from nmCRPC that has developed resistance to treatment, said Small. He continued: “Since it’s well established that metastases are a major cause or morbidity and mortality in men with prostate cancer, and there are no approved therapies for patients with nmCRPC, the prevention of metastases represents an important, unmet medical need.”
Apalutamide is an orally administered next-generation androgen receptor inhibitor with antitumor activity in CRPC. Small and his research team evaluated the effects of apalutamide on MFS in men with nmCRPC in the SPARTAN trial, a phase 3, double-blind, randomized study of apalutamide versus placebo in patients with nonmetastatic castrate resistant prostate cancer.
Patients with nmCRPC and prostate-specific antigen doubling time (PSADT) of 10 months or less were randomized 2:1 to be administered 240 mg once daily of apalutamide or placebo on a continuous dosing daily regimen. Disease assessments were performed every 16 weeks. The primary endpoint of the study was MFS, which the researchers defined as the time from randomization to first radiographic distant metastasis or death.
Secondary endpoints were listed in hierarchal order; a secondary endpoint had to be statistically significant to move on to testing the next secondary endpoint. They included time to metastasis, progression-free survival (PFS), time to symptomatic progression, and overall survival (OS). The researchers also evaluated second progression-free survival (PFS2), which was defined as the time from randomization to disease progression or death after first treated for mCRPC.
A total of 1207 patients were included in the study and randomized. The baseline PSADT was less than 5 months in each cohort. Results showed that apalutamide reduced the risk of distant metastasis or death by 72% (HR = 0.28; 95% Cl, 0.23-0.35; P <.0001), with a median MFS of 40.5 months for the apalutamide cohort versus 16.2 months for the placebo group.
“The treatment effect of apalutamide on MFS was consistently favorable across all pre-specified subgroups, including prostate-specific antigen (PSA) level and PSADT,” said Small. “The results for the primary endpoint are supported by consistent improvement across all secondary endpoints.”
There was a 73% risk reduction in time to metastasis, a 71% risk reduction in PFS, and a 55% risk reduction in symptomatic progression.
In an interim analysis for OS, there was a trend favoring apalutamide. At a median follow-up of 20.3 months, 61% of apalutamide participants and 30% of placebo participants were still on treatment. The rates of discontinuation due to adverse events were low in both cohorts (10.7% for apalutamide, 6.3% for placebo).
“These data suggest that apalutamide treated in nmCRPC may provide clinical benefit compared with the current standard of using approved treatments after progression to metastatic disease,” concluded Small. “Together with its favorable side effects profile, these efficacy data suggest that apalutamide should be considered as a new standard of care for men with high-risk nmCRPC.”