On May 31, New England Journal of Medicine published the results of the phase III TITAN trial, which were presented at the 2019 ASCO. The study showed the addition of apalutamide to androgen deprivation therapy compared with placebo plus ADT significantly improved the dual primary endpoints of overall survival and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer (mCSPC).
The study included 1,052 patients with mCSPC. They were randomized 1:1 and received either apalutamide (240 mg) plus continuous ADT, or placebo plus ADT. TITAN study included mCSPC patients with both low- and high-volume disease, those who were newly diagnosed, or those who had received prior definitive local therapy or prior treatment with up to six cycles of docetaxel or up to six months of ADT for mCSPC.
Apalutamide increases rPFS in 24 months with rates of 68.2% vs. 47.5% for the placebo group (HR 0.48, 95% CI 0.39-0.60, p <0.001). There was also an increase in OS at 24 months, with rates of 82.4% for the apalutamide group and 73.5% for placebo (HR 0.67, 95% CI 0.51-0.89, p = 0.005). There was no significant increase in toxicities in the apalutamide arm, with cutaneous rash being the single most frequent side effect with antiandrogen, while the incidence of grade 3 or 4 adverse events was similar between the two groups (42.2% apalutamide vs. placebo 40.8% placebo).