Treatment with apalutamide also provided "consistent benefit in other end points, including delaying castration resistance, and health-related quality of life continued to be maintained with an acceptable safety profile," Dr. Kim Chi, with BC Cancer and Vancouver Prostate Center, in Canada, said in a presentation of the data at the American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium.
In the TITAN study, 1,052 men (mean age, 68 years) with mCSPC were randomly allocated to add APA (240 mg once daily) or placebo to ADT. A total of 16% of the patients had undergone prostatectomy or received radiotherapy for localized disease, and 11% had received docetaxel therapy; 63% had high-volume disease, and 37% had low-volume disease.
Results of the first interim analysis were published in The New England Journal of Medicine in 2019 (https://bit.ly/3b32wA3).
At that point, after a median follow-up of 23 months, overall survival (OS) was 82% with APA versus 74% with placebo and radiographic progression-free survival (rPFS) was 68% versus 48%. Compared with placebo, APA significantly reduced the risk of death by 33% (hazard ratio for death, 0.67; P=0.005) and rPFS (HR, 0.48; P<0.001).
The trial was then unblinded, allowing patients in the placebo group without disease progression to crossover to APA. For the final analysis, a preplanned sensitivity analysis for OS accounting for crossover using inverse-probability censoring weighted log-rank test was conducted.
The median treatment duration was 39 months for the APA group, 20 months for the entire placebo group, and 15 months for the group that crossed over to APA.
In the final analysis, after median follow-up of 44 months, APA remained superior to placebo, reducing the risk of death by 35% (P<0.0001), with median OS not reached with APA vs. 52 months with placebo.
The reduction in risk of death increased to 48% after adjusting for the roughly 40% of patients who crossed over from placebo to APA (HR, 0.52; P<0.0001).
"The treatment effect on overall survival favored apalutamide across all prespecified subgroups including those with low- and high-volume disease," Dr. Chi reported.
He noted that other clinically relevant endpoints also favored APA over placebo and the safety profile of APA plus ADT with longer follow-up remained consistent with the primary analysis.
"Importantly, cumulative incidences of any-grade treatment-emergent falls, fractures and fatigue were similar between groups. Grade-3 to -4 treatment-emergent adverse events and serious adverse events were also similar between groups," he said.
"Given this long-term follow-up data from TITAN, showing the substantial overall survival benefit, ease of use and tolerability, it really provides a good option for patients with metastatic castration-sensitive prostate cancer," Dr. Chi said.
The TITAN study was funded by Janssen Research and Development. Dr. Chi and several co-investigators disclosed financial relationships with the company.
SOURCE: https://meetings.asco.org/gu/attend ASCO 2021 Genitourinary Cancers Symposium, presented February 11, 2021.
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