Kim Chi, MD, Vice President & Chief Medical Officer of BC Cancer speaks about TITAN: A final analysis with close to four years of follow-up data evaluating Erleada versus placebo in patients with metastatic castration-sensitive prostate cancer receiving hormone therapy (Abstract #11).
Link to Abstract-
APA or PBO applied to ADT in pts with mCSPC is evaluated by TITAN. Eligibility was made for Pts with high- and low-volume disease, prior docetaxel, prior localized disease therapy, and prior ADT ( ⁇ 6 mos). APA substantially improved the dual primary endpoints of overall survival (OS) (hazard ratio [HR] 0.67) and radiographic progression-free survival (rPFS) (HR 0.48) relative to PBOS (hazard ratio [HR] 0.67) and radiographic progression-free survival (rPFS) (HR 0.48) in the first interim study with 22.7 MB of median follow-up (Chi et al. NEJM. 2019). OS analysis was first scheduled on an interim basis at that time, while rPFS was final. TITAN was unblinded, allowing pts without advancement to cross over to APA, who were still receiving PBO. Here, the final review of TITAN's effectiveness and safety results is published.
To receive APA (240 mg QD) or PBO plus ADT, 1052 mCSPC pts is randomized at 1:1. The Kaplan-Meier process and Cox proportional hazards model evaluated time-to-event endpoints. A pre-planned OS sensitivity analysis was carried out, accounting for crossover using the weighted log-rank test of inverse likelihood censoring (IPCW). No formal statistical retesting was performed; without multiplicity adjustment, nominal p values were recorded. A mixed-effect repeated-measures model was used to test the improvement from the baseline in the Functional Evaluation of Cancer Therapy-Prostate (FACT-P) total score.
405 OS events occurred with a median follow-up of 44 mos. 208 PBO pts (39.5 percent) crossed over to APA after unblinding. The median period of treatment was 39.3 mos for the APA group, 20.2 mos for the whole PBO group, and 15.4 mos for the crossover PBO/APA group. In comparison with the PBO group, OS was superior in the APA group despite crossover (Table). Survival rates of 48-mo were 65 percent (APA) vs 52 percent (PBO). APA vs PBO also preferred other endpoints (Table). Per total FACT-P, health-related quality of life (HRQoL) was preserved through the analysis in the APA community and was not different from the PBO group. Security has been consistent with past studies.
The final study of TITAN showed that APA plus ADT offers an improvement in OS with a 35 percent reduction in risk of death in a large population of pts with mCSPC, which increased to 48 percent reduction after adjustment for pts that crossed from PBO to APA, with nearly 4 years of follow-up. In addition, other endpoints, including delaying castration resistance, had clear advantages with APA, and HRQoL continued to be maintained with a reasonable safety profile. Details on the clinical trial: NCT02489318