Apalutimide in combination with androgen deprivation therapy led to a significant improvement in overall survival in patients with nonmetastatic castration-resistant prostate cancer in the phase 3 SPARTAN clinical trial.
Apalutimide (Erleada) in combination with androgen deprivation therapy (ADT) led to a significant improvement in overall survival (OS) compared with ADT plus placebo in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) in the phase 3 SPARTAN clinical trial, according to findings presented at the 2020 American Society of Clinical Oncology Virtual Scientific Program.1
Apalutimide previously received FDA approval for the treatment of nmCRPC in February of 2018 following an interim analysis that showed significant improvement in metastasis-free survival (MFS).
“This final analysis of SPARTAN demonstrated that apalutimide significantly improved survival in men with nonmetastatic castration-resistant prostate cancer,” said lead author and presenter Eric J. Small, MD, of the University of California San Francisco Helen Diller Family Comprehensive Cancer Center. “And it did so despite a high rate of subsequent active therapy in the placebo group.”
At a follow up of 52.0 months, 428 of a required 427 OS events had occurred. Median OS for the apalutimide plus ADT group was 73.9 months vs 59.9 months for the ADT plus placebo (HR, 0.784; P = .0161). Apalutimide also significantly increased time to cytotoxic chemotherapy (HR, 0.629; P = .0002) when compared with the placebo arm.
The SPARTAN trial enrolled 1207 patients who were then randomized 2:1 to either apalutimide versus placebo, with a primary end point of MFS defined as the time from randomization to the first detection of distant metastasis on imaging or death. Primary analysis showed that treatment with apalutimide significantly improved metastasis-free survival (40.5 months vs 16.2 months, respectively) and time to symptomatic progression (HR, 0.45; 95% CI, 0.32-0.63; P < 0.001).2
Following the release of those data, and at the recommendation of an independent data monitoring committee, the study was unblinded and all 76 eligible placebo patients crossed over to receive apalutimide.
The safety profile of apalutimide remained consistent with prior interim analyses even with substantially longer time of follow up, with 55.9% (n = 449) of patients reporting grade 3 or 4 treatment-related adverse events (AEs). Serious AEs were reported by 290 patients (36.1%), with 120 patients (14.9%) reporting AEs that lead to treatment discontinuation.
The most frequently reported AEs of any grade were fatigue (32.6%), hypertension (28.0%), and diarrhea (23.3%). Among grade 3 or 4 AEs, hypertension was most common (16.3%). Additional grade 3 or 4 AEs included skin rash (5.2%), fractures (4.9%), falls (2.7%) and ischemic heart disease (2.6%). The rates of these events did not change substantially after the first and second interim analyses.
Treatment discontinuation due to AEs was more common in apalutimide vs placebo, and 1 AE leading to death (resulting from myocardial infarction) was considered potentially related to apalutimide treatment.