medwireNews: Supplementing androgen deprivation therapy (ADT) with apalutamide leads to significant improvements in survival outcomes in men with metastatic castration-sensitive prostate cancer (CSPC), show phase III trial results.
As reported simultaneously at the 2019 ASCO Annual Meeting in Chicago, Illinois, USA, and in The New England Journal of Medicine, the co-primary endpoints of radiographic progression-free survival (PFS) and overall survival (OS) were significantly improved for the 525 trial participants who received apalutamide 240 mg/day alongside ADT relative to the 527 men who instead received placebo plus ADT.
Specifically, in the double-blind TITAN (Targeted Investigational Treatment Analysis of Novel Anti-androgen) trial, the 24-month radiographic PFS rate was 68.2% for the apalutamide group and 47.5% for the placebo group, giving a significant hazard ratio (HR) for radiographic progression or death of 0.48. The median radiographic PFS duration was unreached and 22.1 months, respectively.
The 24-month OS rate was likewise significantly higher among apalutamide- than placebo-treated men, at 82.4% versus 73.5%, and the HR for death was 0.67 in favor of the androgen receptor inhibitor. Median OS was unreached in both treatment arms in this first interim analysis conducted at a median follow-up of 22.7 months.
Kim Chi (BC Cancer and Vancouver Prostate Centre, British Columbia, Canada) and fellow TITAN investigators note that subgroup analyses consistently favored apalutamide, including among patients with high or low volume of disease, those with de novo or relapsed metastatic disease, and regardless of prior docetaxel use. But they acknowledge “the limitation that certain patient subgroups were relatively small.”
The team adds that in light of these results “the independent data-monitoring committee recommended unblinding to allow crossover of patients receiving placebo to receive apalutamide.”
With regard to the safety profile, the incidence of grade 3 or 4 adverse events (AEs) and severe AEs was similar across the apalutamide and placebo groups, at 42.2% versus 40.8% and 19.8% versus 20.3%, respectively. AEs led to discontinuation in 8.0% of apalutamide-treated patients and 5.3% of those given placebo, and to death in a respective 1.9% and 3.0%.
Rash was the most common AE of special interest in the apalutamide arm, both at any grade (27.1 vs 8.5% for placebo) and at grade 3 or worse (6.3 vs 0.6%)
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