In findings from the phase III SPARTAN trial presented at the 2018 Genitourinary Cancers Symposium and published in the <em>New England Journal of Medicine, </em>apalutamide (Erleada) reduced the risk of metastasis or death by 72% in patients with nonmetastatic castration-resistant prostate cancer.
Eric J. Small, MD
In findings from the phase III SPARTAN trial presented at the 2018 Genitourinary Cancers Symposium and published in theNew England Journal of Medicine,apalutamide (Erleada) reduced the risk of metastasis or death by 72% in patients with nonmetastatic castration-resistant prostate cancer (CRPC).1,2Median metastasis-free survival (MFS) was 40.5 months with apalutamide versus 16.2 months in the placebo arm (HR, 0.28; 95% CI, 0.23-0.35; P<.0001).
Based on these data, the FDA granted a priority review to apalutamide for use in this setting. The agency is scheduled to make its final decision by the end of April 2018.
“Overall, these data suggest that apalutamide should be considered as a new standard of care for men with high-risk nonmetastatic castration-resistant prostate cancer,” said lead study author Eric J. Small, MD, professor of medicine at the University of California, San Francisco.
“Apalutamide is a next-generation competitive inhibitor of the androgen receptor under development for the treatment of patients with prostate cancer,” explained Small. The drug “prevents binding of androgens to the androgen receptor and the translocation of the androgen receptor to the nucleus, and impedes androgen receptormediated DNA transcription,” he added.
The SPARTAN trial evaluated the safety and efficacy of apalutamide versus placebo in 1207 patients with nonmetastatic CRPC and a rapidly rising prostate specific antigen (PSA) level despite receiving continuous androgen deprivation therapy. Nonmetastatic status was determined by a negative bone scan, as well as a negative CT of the pelvis, abdomen, chest, and brain.
Patients were required to have a PSA doubling time of ≤10 months, since “prior data has shown that these are the patients most at risk for developing metastases and death,” said Small.
Patients were randomized in a 2:1 ratio to 240 mg of apalutamide daily (n = 806) or placebo (n = 401). The average baseline PSA doubling time was less than 5 months in both arms. Patients who developed metastases were allowed to receive abiraterone acetate (Zytiga) plus prednisone, which Small noted is the standard of care in patients with metastatic CRPC.
Beyond the primary MFS endpoint, secondary endpoints included time to metastasis, progression-free survival (PFS), time to symptomatic progression, and overall survival (OS). For patients who developed metastases, the researchers also evaluated the time between randomization to first treatment for metastatic CRPC and subsequent progression (PFS2).
The median PFS was 40.5 months in the apalutamide arm compared with 14.7 months in the placebo arm (HR, 0.29; 95% CI, 0.24-0.36;P<.001).
At a median follow-up of 20.3 months, 61% of the apalutamide arm remained on treatment compared with 30% of the placebo group. An interim OS analysis (24% of events) revealed a trend favoring apalutamide (HR, 0.70; 0.47-1.04;P= .07), although the median OS was not yet reached in the apalutamide arm.
Adverse events led to discontinuation in 10.7% and 6.3% of the apalutamide and control arms, respectively. Rash (23.8% vs 5.5%), hypothyroidism (8.1% vs 2.0%), and fracture (11.7% vs 6.5%) all occurred more frequently in the apalutamide arm compared with the placebo arm, respectively. Neither group had a reduction in mean baseline health-related quality-of-life scores as the trial progressed, and there was no difference over time in the scores between the groups.
Eighty percent of placebo patients who progressed and 56% of apalutamide patients were treated for metastatic CRPC. The researchers noted that PFS2 was longer for patients who were initially randomized to apalutamide.
"Delaying the metastasis of prostate cancer is critical. Once the cancer starts to spread, the patient's overall health, well-being and prognosis change drastically," said Peter Lebowitz, MD, PhD, global therapeutic area head of oncology at Janssen Research & Development, LLC, said in a statement. "The ERLEADA™ data presented at ASCO GU demonstrate the important impact this medicine can have for patients with prostate cancer. Janssen is committed to addressing unmet needs for treatment across all stages of disease progression with novel combinations and novel therapeutics."