Kim Chi, MD, BC Cancer Centre - Vancouver, Vancouver Prostate Centre, discusses final analysis results from the phase 3 TITAN clinical trial of apalutamide versus placebo for patients with metastatic castration-sensitive prostate cancer (CSPC) receiving androgen deprivation therapy (ADT). These data were presented at the 2021 Virtual ASCO Genitourinary Cancers Symposium. 

Transcript

Hello, I am Dr. Kim Chi, Medical Oncologist at the BC Cancer, Vancouver Cancer Center and at the Vancouver Prostate Center. I am pleased to talk to you about the TITAN trial, the final results which we presented at the 2021 GU Cancer Symposium.

The TITAN study is an international randomized, double-blind, placebo-controlled, phase 3 study that enrolled a broad population of patients with metastatic, castration-sensitive prostate cancer. 1,052 patients were randomized one-to-one to receive either apalutamide or a placebo in addition to standard androgen deprivation therapy.

The dual primary endpoints were radiographic progression-free survival and overall survival. We reported on the primary analysis in 2019, which were published in the New England Journal of Medicine, where both our PFS and OS met statistical significance.

Because of these positive results, the Titan study was unblinded at that time on the recommendation of the independent data safety monitoring committee, and 40% of patients in the placebo group who had not progressed crossed over to receive open-label apalutamide.

At the 2021 GU Cancer Symposium, we presented the final event-driven overall survival analysis, which is conducted at a median follow-up of 44 months, and after 405 events had occurred. In the final analysis, the risk of death with apalutamide was reduced by 35%, so a hazard ratio of 0.65, with a p-value of less than 0.0001.

This hazard ratio is very similar to the hazard ratio of 0.67 at the primary analysis of TITAN, despite the almost 40% of patients crossing over from placebo to apalutamide.

After adjusting for crossover in a preplanned sensitivity analysis, the effect of apalutamide on overall survival increased, with a hazard ratio of 0.52, indicating a reduction in the risk of death by 48%, compared with placebo.

The treatment effect on overall survival favored apalutamide across all the prespecified subgroups. Treatment with apalutamide was also favored in a variety of other endpoints, including significantly prolonging second progression-free survival, or PFS2, and delaying development of castration resistance.

Quality of life was no different between the apalutamide plus ADT and placebo plus ADT groups, and there was no new safety signals. Importantly, the cumulative incidence of adverse events were also similar between the apalutamide and placebo groups, except for rash, which is a known side effect with apalutamide.

What this final analysis confirms is that there is a substantial long-term survival benefit of apalutamide added to ADT across a broad spectrum of patients with metastatic, castrate-sensitive prostate cancer, even with 40 percent of patients crossing over from placebo.

The true benefit may even be greater, with a hazard ratio of 0.52 identified in a sensitivity analysis accounting for that crossover. This is one of the highest reported benefits among the studies evaluating ADT-intensified therapy to date.

This data reinforces that ADT therapy alone is no longer a standard of care for patients with metastatic, castration-sensitive prostate cancer, and apalutamide is one of the treatments of choice, given its efficacy, ease of use, and tolerability.