While multiple phase III studies have demonstrated improved outcomes for metastatic castration-sensitive prostate cancer (mCSPC) patients when androgen signaling inhibitors or docetaxel is added to standard androgen deprivation therapy (ADT), new combinations are not readily used due to safety concerns and lack of long-term follow up.
The results from the final analysis of a 4-year follow-up of the TITAN study recently published in the Journal of Clinical Oncology provide clinical evidence of efficacy and safety for the use of apalutamide plus ADT.
TITAN was an international phase III, randomized, double-blind, placebo-controlled study, with patients assigned 1:1 to receive apalutamide or a matched placebo in addition to continuous ADT. The primary endpoints were overall survival (OS) and radiographic progression free survival (rPFS). After the first prespecified interim analysis for OS and final analysis for rPFS, the patients were unblinded and 208 patients in the placebo group without disease-progression crossed over to receive apalutamide. 49% of the apalutamide group and 67.9% of placebo group discontinued the trial, most commonly due to disease progression.
Risk of death was decreased by 35% with apalutamide compared to placebo. At 48 months the OS rates were 65.1% in the apalutamide group and 51.8% in the placebo treated group. When statistically corrected for crossover effect, the benefit of apalutamide was further confirmed with an OS that reduced the risk of death by 48% and survival rates of 65.2% in the apalutamide group compared to only 37.9% in the placebo.
The risk of initiating cytotoxic chemotherapy was reduced by 53% with apalutamide treatment. Furthermore, apalutamide treatment demonstrated a 66% reduction in the risk of castration resistance and also delayed the onset of castration resistance. Treatment-emergent adverse events were similar between treatment groups, with the most common being rash and fatigue with apalutamide treatment. There were no treatment-related deaths.
There still remains a need for treatment options for patients with prostate cancer, the results of the TITAN study provide evidence for intensified ADT treatment with the early addition of apalutamide for patients with mCSPC. At MEDSIR we are also investigating treatment options for prostate cancer with our study, EXCAAPE. To learn more about our prostate cancer trial or any of our other clinical trials contact us!