SPARTAN Trial: Metastasis-Free Survival in Nonmetastatic Castration-Resistant Prostate Cancer
As reported by Smith et al in The New England Journal of Medicine, the phase III SPARTAN trial has shown that the androgen receptor inhibitor apalutamide (Erleada) produces significant improvement in metastasis-free survival and time to symptomatic progression vs placebo among men with nonmetastatic castration-resistant prostate cancer. The trial supported the recent U.S. Food and Drug Administration approval of apalutamide in this setting.
Study Details
In the double-blind trial, 1,207 patients with a prostate-specific antigen doubling time of ≤ 10 months from 332 sites in 26 countries in North America, Europe, and the Asia-Pacific region were randomized 2:1 between October 2013 and December 2016 to receive apalutamide at 240 mg per day (n = 806) or placebo (n = 401). All the patients continued to receive androgen-deprivation therapy. The primary endpoint was metastasis-free survival, defined as time from randomization to first detection of distant metastasis on imaging or death.
Metastasis-Free Survival
The final analysis for metastasis-free survival was performed after distant metastasis or death had occurred in 378 patients, including 184 (22.8%) in the apalutamide group and 194 (48.4%) in the placebo group. Median metastasis-free survival was 40.5 vs 16.2 months (hazard ratio [HR] = 0.28, P < .001).
In July 2017, an independent data and safety monitoring committee recommended the trial be unblinded and patients in the placebo group be offered the option to receive apalutamide. Among patients with metastases, 60.5% in the apalutamide group and 54.4% in the placebo group had bone metastases. The benefit of apalutamide on metastasis-free survival was consistent across patient subgroups.
Time to symptomatic progression was longer with apalutamide (HR = 0.45, P < .001), with median duration not being reached in either group. Median progression-free survival (40.5 vs 4.7 months, HR = 0.29, P < .001) and median second progression-free survival (not reached vs 39.0 months, HR = 0.49, 95% confidence interval = 0.36–0.66) were prolonged in the apalutamide group.
Adverse Events
Adverse events of any grade occurring more frequently in the apalutamide group vs the placebo group were rash (23.8% vs 5.5%), hypothyroidism (8.1% vs 2.0%), and fracture (11.7% vs. 6.5%). Grade 3 or 4 adverse events occurred in 45.1% vs 34.2% of patients, with the most common in both groups being hypertension (14.3% vs 11.8%).
Serious adverse events occurred in 24.8% and 23.1%, respectively. Adverse events led to discontinuation of study treatment in 10.6% vs 7.0%.
The investigators concluded, “Among men with nonmetastatic castration-resistant prostate cancer, metastasis-free survival and time to symptomatic progression were significantly longer with apalutamide than with placebo.”
The study was funded by Janssen Research and Development.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
