Apalutamide added to androgen deprivation therapy (ADT) for metastatic castration-sensitive prostate cancer (mCSPC) prolongs radiographic progression-free and overall survival regardless of disease volume, according to a final analysis of data from the TITAN phase 3 trial presented at the 36th annual European Association of Urology congress.
The TITAN trial included 1052 men with mCSPC randomly assigned to receive apalutamide 240 mg/d or placebo plus ADT. Findings from the first interim analysis of TITAN after a median 22.7 months of follow-up, which were published in The New England Journal of Medicine in 2019, showed apalutamide-treated patients had a significant 52% decreased risk for radiographic progression and 33% decreased risk for death compared with placebo.
In a final analysis focusing on outcomes according to disease volume, Simon Chowdhury, MD, of Guy’s and St. Thomas’ NHS Foundation Trust in London, UK, and colleagues found that, at a median follow-up of 22.7 months, apalutamide-treated patients with high- and low-volume disease had a significant 48% and 64% improvement in radiographic progression-free survival, respectively, compared with placebo recipients.
At a median follow-up of 44 months, apalutamide-treated patients with high- and low-volume disease had a significant 30% and 47% decreased risk for death, respectively, compared with the placebo group, Dr Chowdhury reported in an oral presentation.
In addition, compared with placebo recipients, apalutamide-treated patients with high- and low-volume disease had a significant 68% and 85% decreased risk for PSA progression, respectively, and 60% and 77% decreased risk for development of castration-resistant disease, respectively.
The investigators noted that the long-term treatment effect of apalutamide was observed even though around 40% of patients crossed over from placebo to apalutamide after unblinding.
At baseline, 63% of patients had high-volume disease and 37% had low-volume disease. The apalutamide group had 325 patients with high-volume disease and 200 with low-volume disease; the placebo group had 335 patients with high-volume disease and 192 with low-volume disease.
The investigators defined high-volume disease as the presence of visceral metastases and 1 or more bone lesions or 4 or more bone lesions with 1 or more outside the vertebral column or pelvis; they defined low-volume disease as the presence of bone lesions not meeting the high-volume definition.
The safety profile of apalutamide in patients with high- and low-volume disease was consistent with the safety profile in the intent-to-treat population as described in earlier reports.
Chowdhury S, Bjartell A, Merseburger AS, et al. Apalutamide for metastastic castration-sensitive prostate cancer: Outcomes in high-volume and low-volume disease from the TITAN final analysis. Presented at: EAU 2021, July 8-12, 2021. Abstract P0845
Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med. 2019;381:13-24. doi:10.1056/NEJMoa1903307