Daniel P. Petrylak, MD, discusses the design and results of the TITAN trial of apalutamide in patients with metastatic castration-sensitive prostate cancer.
Daniel P. Petrylak, MD, professor of medicine and urology at Yale School of Medicine and coleader of Cancer Signaling Networks at Yale Cancer Center, discusses the design and results of the TITAN trial (NCT02489318) of apalutamide (Erleada) in patients with metastatic castration-sensitive prostate cancer (mCSPC).
The phase 3 TITAN trial randomized 1052 patients with mCSPC to receive 240 mg of apalutamide orally once daily or matching placebo both with androgen deprivation therapy (ADT). Patients were eligible if they had at least 1 bone metastasis with prior treatment limited to 6 cycles of docetaxel for mCSPC and if the last dose was up to 2 months prior to randomization. Patients were stratified based on having a Gleason score of 7 or higher versus lower than 7, geographic location in the United States or European Union versus elsewhere, and whether or not patients had received prior docetaxel.
The primary end points were radiographic progression-free survival (rPFS) based on CT or MRI, and overall survival (OS), each for up to 54 months, Petrylak says. Secondary end points included time to pain progression and time to initiation of cytotoxic chemotherapy.
According to Petrylak, at the interim analysis at 22 months, OS was improved with apalutamide with a hazard ratio (HR) of 0.67, and rPFS also increased with a HR of 0.48. At 48 months, the rate of OS with apalutamide was 65% compared with 52% with placebo. There was crossover of 208 patients (39.5%) from the placebo group following the interim results.
0:08 | The TITAN trial randomized 1052 patients who are castration sensitive. They had to have at least 1 lesion on bone scan or a CT scan. And they were allowed to have prior docetaxel and they had to be on ADT for castration-sensitive disease and those who started [must have received it] for less than 6 months. And they're stratified based on Gleason score, geography, as well as [whether] they've had prior docetaxel, and [were] randomized in a 1:1 basis to apalutamide, at 240 mg or placebo. And as I mentioned before, this trial did hit its OS benchmark: 33% reduction in the risk of death as well as a 52% reduction in rPFS.