The Food & Drug Administration (FDA) recently expanded its approval of apalutamide (Erleada) to be included as an add-on treatment of metastatic castration-sensitive prostate cancer (mCSPC) in conjunction with androgen deprivation therapy (ADT). Erleada is manufactured by Janssen, of Johnson & Johnson. The drug was approved for the treatment of nonmetastatic castration-resistant prostate cancer in 2018. The most recent indication follows the phase III TITAN trial, the results of which were published in the New England Journal of Medicine.
The drug will likely compete against enzalutamide (Xtandi, from Pfizer and Astellas) with this new indication. Xtandi is currently indicated for nonmetastatic castration-resistant prostate cancer. It was recently granted priority review by the FDA to determine if it is qualified to treat mCSPC, with a decision expected in 2020.
Efficacy/Outcomes
In the TITAN trial, patients were randomized to receive apalutamide 240 mg/day or placebo in combination with ADT. The primary outcomes were progression-free survival (PFS) and overall survival (OS). After a median 22.7 months of follow-up, the rate of PFS was 68.2% in the apalutamide group and 47.5% in the placebo group, and the rates of OS were 82.4% and 73.5%, respectively.
Enzalutamide was tested in ARCHES, also a phase III study. Patients were randomized to receive enzalutamide 160 mg/day or placebo in combination with ADT. The primary outcome was PFS. The researchers reported: “As of October 14, 2018, the risk of radiographic progression or death was significantly reduced with enzalutamide plus ADT versus placebo plus ADT (hazard ratio, 0.39; 95% CI, 0.30 to 0.50; P < .001; median not reached v 19.0 months).”
Enzalutamide was also tested in ENZAMET, another randomized, phase III study. Patients received testosterone suppression plus either enzalutamide or a standard nonsteroidal antiandrogen therapy. The primary outcome was OS, and one of the secondary outcomes was PFS. After a median follow-up of 34 months, there were 102 deaths in the enzalutamide group and 143 in the standard-care group (HR, 0.67; 95% confidence interval [CI], 0.52 to 0.86; P = 0.002). Overall three-year survival estimates were 80% in the enzalutamide group and 72% in the standard-care group. Enzalutamide was superior in PFS (174 and 333 events, respectively; HR, 0.39; P < 0.001).
Safety
In the TITAN trial, the rates of grade 3 or 4 adverse events were similar in the apalutamide (42.2%) and placebo (40.8%) groups; the study authors noted that the apalutamide group had a higher rate of rash.
The ARCHES trial also found a similar rate of grade 3 or greater adverse events in the treatment (24.3%) and placebo (25.6%) groups.
In ENZAMET, patients were more likely to discontinue enzalutamide due to adverse events than standard care. Enzalutamide patients were more prone to fatigue, and there were seven seizures in the enzalutamide group and zero in the standard care group.
Cost
A 30-day supply of Erleada costs an estimated $12,297. A one-month supply includes 120 60-mg pills. The recommended daily dose is 240 mg.
A 30-day supply of Xtandi costs an estimated $12,066. A one-month supply includes 120 40-mg pills. The recommended daily dose is 160 mg.
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