Literature
Clinical Pearls & Morning Reports
Published April 11, 2018
How effective is apalutamide as compared to placebo in men with nonmetastatic castration-resistant prostate cancer?
Metastases are a major cause of complications and death among men with prostate cancer. Prevention of metastases to bone and other sites represents an important treatment goal. Smith et al. conducted the international phase 3 SPARTAN trial to evaluate the effect of apalutamide on metastasis-free survival in men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen (PSA) doubling time of 10 months or less. Patients were randomly assigned, in a 2:1 ratio, to receive apalutamide or matched placebo. Androgen-deprivation therapy was continued throughout the trial. Read the latest NEJM Original Article here.
Clinical Pearls
Q: What is apalutamide?
A: Apalutamide is a nonsteroidal antiandrogen agent that is under development for the treatment of prostate cancer. Apalutamide binds directly to the ligand-binding domain of the androgen receptor and prevents androgen-receptor translocation, DNA binding, and androgen-receptor–mediated transcription.
Q: What is the mainstay of treatment for metastatic prostate cancer?
A: Androgen-deprivation therapy — either bilateral orchiectomy or treatment with a gonadotropin-releasing hormone analogue agonist or antagonist — is the mainstay of treatment for metastatic prostate cancer. Androgen-deprivation therapy is also an important part of care for many men with nonmetastatic prostate cancer. Although androgen-deprivation therapy is initially effective, castration-resistant disease eventually develops in almost all men with prostate cancer. Among men with nonmetastatic castration-resistant prostate cancer, a shorter PSA doubling time is associated with a shorter time to metastasis or death.
Morning Report Questions
Q: How effective is apalutamide as compared to placebo in men with nonmetastatic castration-resistant prostate cancer?
A: In the SPARTAN trial, involving men with nonmetastatic castration-resistant prostate cancer, the risk of metastasis or death was more than 70% lower with apalutamide than with placebo, and the median metastasis-free survival was more than 2 years longer (40.5 months vs. 16.2 months). The effect was observed across all subgroups, including patients in all age groups, those with short PSA doubling times, and those with local or regional nodal disease at trial entry. Time to metastasis, progression-free survival, and time to symptomatic progression were significantly longer with apalutamide than with placebo.
Q: What adverse events were more common with apalutamide than with placebo in the SPARTAN trial?
A: Apalutamide was associated with higher rates of rash, fatigue, arthralgia, weight loss, falls, and fracture than placebo. The majority of adverse events were grade 1 or 2. Disease progression was the most common reason for discontinuation of the trial regimen in both groups.