The FDA approved apalutamide (Erleada, Janssen Biotech, Inc.) to treat patients with nonmetastatic castration-resistant prostate cancer.
Androgen-deprivation therapy (ADT) is an effective and integral part of care for patients with nonmetastatic prostate cancer. However, resistance to ADT is inevitable and develops in almost all cases of prostate cancer. Preventing metastasis to bone and other sites is an important goal in treatment. Apalutamide is a nonsteroidal antiandrogen agent that has been found to increase the time until metastasis in prostate cancer. It works by binding directly to the ligand-binding domain of the androgen receptor, and preventing processes such as receptor translocation, DNA binding, and transcription.
Approval of apalutamide was based on data from SPARTAN, a multicenter double-blind placebo-controlled phase 3 trial involving 1207 patients with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time ≤10 months on ADT. Patients were randomly assigned in a 2:1 ratio to receive either apalutamide 240 mg orally once daily with ADT or placebo once daily with ADT.
The median metastasis-free survival was 40.5 months in the apalutamide arm and 16.2 months in the placebo arm (hazard ratio for metastasis or death, 0.28; 95% confidence interval [CI], 0.23 to 0.35; P<0.001). Additionally, apalutamide was associated with longer time to metastasis, progression-free survival, and time to symptomatic progression.
The most common adverse events of any grade associated with apalutamide during the SPARTAN trial were fatigue (39%), hypertension (25%), rash (24%), diarrhea (20%), nausea (18%), arthralgia (16%), fall (16%), weight loss (16%), hot flush (14%), fracture (12%), and peripheral edema (11%).
Rash was the most common adverse event that led to discontinuation (3%). Macular or maculopapular rashes occurred at a median of 82 days of treatment and typically resolved within a median of 60 days for most patients. Management of rash included topical and systemic corticosteroids as well as oral antihistamines.
Hypothyroidism occurred in 8% of patients receiving apalutamide. In those already receiving thyroid replacement therapy, apalutamide worsened hypothyroidism. Hypothyroidism was managed with increases in or initiation of thyroid replacement therapy.
Apalutamide is not indicated in females and is contraindicated in pregnancy. Males should use effective contraception during treatment and for 3 months after the last dose of apalutamide. Apalutamide may cause infertility.
Dosing and Cost
The recommended dosing of apalutamide is 240 mg by mouth once daily. If a dose is missed, administer as soon as possible on the same day and return to the normal dosing schedule the following day. Apalutamide is supplied as 60-mg oral tablets which should be swallowed whole. It can be taken with or without food. The estimated price for a 30-day supply of 120 tablets is about $10,000.