Apalutamide significantly prolongs metastasis-free survival and time to symptomatic progression compared with placebo among men with nonmetastatic castration-resistant prostate cancer (CRPC) not susceptible to androgen-deprivation therapy (ADT), according to a study published in The New England Journal of Medicine.
ADT is an effective early therapy for non-metastatic CRPC, but most patients eventually develop castration-resistant disease. A previous study demonstrated that apalutamide prevented elevations of prostate-specific antigen (PSA), a prognostic factor for the development of metastases.
For the SPARTAN phase 3 study, researchers randomly assigned 1207 men characterized as high-risk for developing metastases who had a PSA doubling time for 10 months or less to receive apalutamide 250 mg daily or placebo; all patients continued ADT throughout the study. Eligible patients had castration-resistant disease and were confirmed as not having metastatic disease, local, or regional nodal disease at baseline.
The planned primary analysis ― which was conducted after 378 events occurred — showed that the median metastasis-free survival among patients in the apalutamide arm was 40.5 months compared with 16.2 months in the placebo arm (P < .001).
Patients treated with apalutamide also had a significantly prolonged median time to symptomatic progression, progression-free survival, and time to metastasis, compared with placebo (P < .001).
Adverse events that were observed more frequently in the apalutamide arm included rash, hypothyroidism, and fracture.
The authors concluded that “among men with nonmetastatic castration-resistant prostate cancer, metastasis-free survival was significantly longer with apalutamide than with placebo. Consistent improvements in secondary and exploratory end points provide support for the veracity of our primary finding.”
Smith MR, Saad F, Chowdhury S, et al. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med. 2018 Feb 8. doi: 10.1056/NEJMoa1715546 [Epub ahead of print]