We just returned from the very busy American Society of Clinical Oncology (ASCO) conference, which was held in Chicago. Although there was not a lot of new information released at the meeting for prostate cancer, there were a few points worth our reporting on, which we will do over the upcoming week.
The first pertained to the newly approved drug for M0 prostate cancer, apalutamide (Erleada). According to the data released from the TITAN TRIAL, which evaluated the combination of apalutamide plus ADT against ADT alone in hormone sensitive progressing prostate cancer:
• Apalutamide improved radiographic progression-free survival, with a 52% reduction in risk of death or radiographic progression. This benefit was observed across all subgroups of men analyzed.
• Apalutamide also improved overall survival (OS), with a 33% reduction in risk of death.
• The rates of grade 3/4 adverse events (the more severe side effects) were no different; 42% in the apalutamide group and 41% in the placebo group.
• Treatment discontinuation due to adverse events was also low in both the apalutamide and control groups with 8% in the apalutamide group and 5% in the placebo group.
TITAN was a randomized, double-blind, phase III study, where men were randomly assigned 1:1 (regardless of the extent of disease) to apalutamide at 240 mg/d or placebo, added to ADT, in 28-day cycles. Men with prior treatment for localized disease or prior docetaxel for metastatic castration-sensitive prostate cancer were allowed, and all patients received continuous ADT.
The median age was 68 years; 8% of the men had prior treatment(s) for localized disease; 11% had received prior docetaxel; and 63% and 37% had high- or low-volume disease, respectively. The primary endpoints were radiographic progression-free and overall survival.
When the data were examined at 22.6-months, 66% of men in the apalutamide group, and 46% of the men in the placebo group remained on treatment.
They found that the use of apalutamide improved radiographic progression-free survival with a 52% reduction in risk of death or radiographic progression; that benefit was observed across all subgroups analyzed. The median radiographic progression-free survival was not reached in the apalutamide group and was 22.1 months in the placebo group.
Apalutamide also improved overall survival with a 33% reduction in risk of death. Median overall survival was not reached in the apalutamide or placebo groups.
Also, time to initiation of cytotoxic chemotherapy (Taxotere or Jevtana) was significantly improved. Based on these results, the independent data monitoring committee recommended unblinding to allow crossover of patients receiving placebo to receive apalutamide.
The investigators concluded (Chi, et. Al.), “In the TITAN study in men with metastatic castration-sensitive prostate cancer, including patients with high- and low-volume disease and prior docetaxel, addition of apalutamide to ADT significantly improved [radiographic progression-free survival] and [overall survival], and the safety profile was tolerable. These results support the addition of apalutamide to ADT for [the] treatment of patients with metastatic castration-sensitive prostate cancer.”