The Janssen Pharmaceutical Companies of Johnson & Johnson announced that the U.S. Food and Drug Administration (FDA) has approved ERLEADA™ (apalutamide), a next-generation androgen receptor inhibitor, for the treatment of patients with non-metastatic castration-resistant prostate cancer (NM-CRPC). ERLEADA™ is the first FDA-approved treatment for these patients. Today’s approval follows an FDA Priority Review designation based upon data from the Phase 3 SPARTAN study, which demonstrated a 72 percent reduction in risk of distant metastasis or death, and an increase in median metastasis-free survival (MFS) by more than two years (difference of 24.31 months) in patients with NM-CRPC.
“The need to delay metastasis is critical to the treatment of prostate cancer. Nearly 90 percent of patients with castration-resistant prostate cancer will eventually develop bone metastases, at which point the prognosis sharply worsens,” said Mathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, LLC. “We are excited about what this approval means for patients living with prostate cancer, and that physicians now have an important and much-needed treatment option that has been shown to delay the progression of castration-resistant prostate cancer.”
ERLEADA™ received FDA approval based on the Phase 3 data from the SPARTAN clinical trial, which assessed the efficacy and safety of ERLEADA™ versus placebo in patients with NM-CRPC who had a rapidly rising PSA while receiving continuous androgen deprivation therapy.The study was recently presented at the 2018 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) on Thursday, February 8, 2018 in San Francisco and published in The New England Journal of Medicine.
“The SPARTAN trial results demonstrated impressive clinical benefits in patients with non-metastatic castration-resistant prostate cancer,” said Matthew Smith, M.D., Ph.D., Director of the Genitourinary Malignancies Program at the Massachusetts General Hospital Cancer Center, Professor of Medicine at Harvard Medical School, and co-principal investigator of the SPARTAN study. “As an oncologist and clinical investigator, I know how devastating it can be for patients and their families to hear that the cancer has spread. With this approval, doctors now have the chance to offer hope for delaying metastases in patients with castration-resistant prostate cancer.”
“As the impact of prostate cancer continues to grow, we are reminded every day of the critical need for therapeutic options that offer patients with prostate cancer more time with their loved ones,” Mark Scholz, M.D., Executive Director of the Prostate Cancer Research Institute. “Today’s approval is significant, as it means that patients with non-metastatic castration-resistant prostate cancer now have a treatment option that offers renewed hope.”
SPARTAN, a Phase 3, randomized, double-blind, placebo-controlled, multi-center study, enrolled 1,207 patients with non-metastatic castration-resistant prostate cancer. Patients were randomized 2:1 to receive either ERLEADA™ orally at a dose of 240 mg once daily (n=806), or placebo once daily (n=401). All patients in the SPARTAN trial received a concomitant gonadotropin-releasing hormone (GnRH) analog or had a bilateral orchiectomy.
ERLEADA™ decreased the risk of distant metastasis or death by 72 percent compared to placebo (HR = 0.28; 95% CI, 0.23-0.35; P<0.0001). The median MFS was 40.51 months for ERLEADA™ compared to 16.20 months for placebo, prolonging MFS by more than two years (difference of 24.31 months).4 MFS benefit was consistently seen across patient subgroups including prostate specific antigen doubling time (PSADT) (≤6 months or >6 months), use of a prior bone-sparing agent (yes or no), and locoregional disease (N0 or N1).
The major efficacy outcome was supported by statistically significant improvements for the following secondary endpoints: time to metastasis (TTM), progression-free survival (PFS) and time to symptomatic progression. The median TTM was 40.51 months for ERLEADA™ compared to 16.59 months for placebo (HR=0.27; 95% CI, 0.22-0.34; P<0.0001) and the median PFS was 40.51 months compared to 14.72 months for placebo (HR=0.29; 95% CI, 0.24-0.36; P<0.0001). Overall survival data were not mature at the time of final MFS analysis (24% of the required number of events).
Warnings and Precautions include seizure, falls and fractures. In the SPARTAN trial, the most common adverse reactions (≥10%) were fatigue, hypertension, rash, diarrhea, nausea, weight decreased, arthralgia, fall, hot flush, decreased appetite, fracture, and peripheral edema.
