By Mary Ellen Schneider
Adding apalutamide to androgen deprivation therapy (ADT) significantly improved overall survival for patients with metastatic castration-sensitive prostate cancer (mCSPC) over ADT alone, according to findings reported at the American Society of Clinical Oncology’s 2021 Genitourinary Cancers Symposium.
The findings come from the final analysis of the TITAN trial, which after four years of follow up showed a 35% lower risk of death with the one-two punch of apalutamide and ADT, compared with placebo plus ADT (Abstract 11).
“These results confirmed the favorable benefit-risk profile of apalutamide,” said Kim N. Chi, MD, of BC Cancer and Vancouver Prostate Centre, who presented the study findings.
The international, phase 3 trial randomized 1,052 patients with mCSPC to either apalutamide or placebo, plus ADT. The researchers reported the study’s primary analysis in 2019, showing that both radiographic progression-free survival and overall survival met statistical significance after 22.7 months of follow up. At the time of the primary analysis, the independent data monitoring committee recommended unblinding the study. As a result, 39.5% of patients in the placebo group, who had not progressed, crossed over to receive open label apalutamide.
In the primary analysis, which was published in the New England Journal of Medicine, researchers reported a 33% reduced risk of death and a 52% reduced risk of radiographic progression or death.
In the final analysis, presented at the 2021 Genitourinary Cancers Symposium, the median treatment duration in the apalutamide group was 39.3 months, compared with 20.2 months in the placebo group. Among patients who crossed over from placebo to apalutamide, the median treatment duration on apalutamide was 15.4 months.
Overall, the final analysis showed a 35% lower risk of death for the apalutamide arm, compared with placebo. The median overall survival was not reached in the apalutamide arm and was 52.2 months in the placebo arm (Hazard Ratio [HR] 0.65; 95% CI: 0.53-0.79; P < 0.0001). “This hazard ratio was similar to the hazard ratio of 0.67 at the primary analysis of TITAN, despite the almost 40% crossover rate of the placebo group to apalutamide,” Dr. Chi said.
After completing the prespecified crossover adjustment, the overall survival benefit improved, with a reduced risk of death of 48% (HR 0.52; 95% CI: 0.42-0.64; P < 0.0001).
Apalutamide also delayed the time to castration resistance, compared with placebo plus ADT. The median time to castration resistance was not reached in the apalutamide group and was 11.4 months in the placebo group (HR 0.34; 95% CI: 0.29-0.41; P < 0.0001).
The treatment effect on overall survival favored apalutamide across several prespecified subgroups, including patients with low- and high-volume disease, Dr. Chi said. The one exception was patients who had received prior docetaxel. “However, this subgroup comprised only 10% of patients and among them, there have been relatively few events,” he said.
A post-hoc interaction analysis between treatment and prior use of docetaxel showed no significant interaction, he said.
In the final analysis, the safety profile remained consistent with earlier reports from the trial. Any grade treatment-emergent adverse events (TEAEs) occurred in more than 95% of patients in both arms of the study. The most common TEAE was rash, which was elevated in the apalutamide group but reached a plateau after about 6 months, Dr. Chi said.