The European Medicines Agency’s Committee for Medicinal Products for Human Use granted support for approval of apalutamide for the treatment of adult patients with nonmetastatic castration-resistant prostate cancer who are at high risk of developing metastatic disease.
Ivo Winiger-Candolfi, MD
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) granted support for approval of apalutamide (Erleada) for the treatment of adult patients with nonmetastatic castration-resistant prostate cancer (CRPC) who are at high risk of developing metastatic disease, according to Janssen Pharmaceutical Companies, the developer of apalutamide, which announced the decision in a news release.1
“We are pleased with the CHMP’s decision to recommend approval of apalutamide for the treatment of patients with [nonmetastatic] CRPC,” said Ivo Winiger-Candolfi, MD, Janssen Oncology Solid Tumor Therapy Area Lead, Europe, Middle East and Africa, Cilag GmbH Internation, in the release. “We know that each prostate cancer patient journey is unique and today’s positive CHMP opinion brings us one step closer to offering patients an effective treatment option that delays the spread of their disease.”
In February 2018, apalutamide, a next-generation oral androgen receptor inhibitor, became the first drug to receive approval from the FDA for use in nonmetastatic CRPC. Following this decision, the inhibitor was also approved in Canada, Australia, Argentina, and Brazil, for this indication.
The CHMP’s positive opinion, as well as the FDA approval, are based on data yielded from the phase III SPARTAN trial, which evaluated the safety and effectiveness of apalutamide compared with placebo in patients with nonmetastatic CRPC who have a rapidly rising prostate specific antigen (PSA) level, despite receiving continuous androgen deprivation therapy (ADT).
The major efficacy endpoint for the trial was metastasis-free survival (MFS), which was defined as time from randomization to the time of first evidence of distant metastasis or death due to any cause.
The results of SPARTAN demonstrated that, when added to ADT, apalutamide significantly reduced the risk of developing distant metastasis or death by 72% compared with placebo in combination with ADT (HR, 0.28; 95% CI, 0.23-0.35; P <.001).2 Improvement in the median MFS over 2 years (40.5 months vs 16.2 months, respectively) was observed in patients with nonmetastatic CRPC whose PSA is rapidly rising.
The multicenter, double-blind trial included 1207 patients with nonmetastatic CRPC who were randomized 2:1 to receive either 240 mg of oral apalutamide in combination with ADT once daily (n = 806) or placebo once daily with ADT (n = 401).
The most common grade 3/4 treatment-emergent adverse events (AEs) observed in the phase III trial included hypertension (14.3% with apalutamide vs 11.8% with placebo), rash (5.2% vs 0.3%), fall (1.7% vs 0.8%), and fracture (2.7% vs 0.8%). Eleven percent of those who received apalutamide discontinued treatment due to AEs compared with 7% of those in the placebo arm. Rates of those who experienced serious AEs were comparable between arms (25% vs 23%, respectively).
“Data from the SPARTAN study showed that apalutamide significantly improves MFS for patients with castration-resistant prostate cancer,” stated Simon Chowdhury, MA, MBBS, MRCP, PhD, a consultant medical oncologist at Guy’s and St. Thomas’ Hospitals, in the release. “Nearly 90% of patients with castration-resistant prostate cancer will eventually develop bone metastases. At that point, their prognosis worsens dramatically. Delaying the spread of cancer is, therefore, critical for patients living with prostate cancer.”