Loading ...

TOPLINE:

In a pooled analysis of the SPARTAN and TITAN trials, statin use during apalutamide therapy was associated with superior overall survival (OS) but also with an increased risk for grade 3 or greater cardiac adverse events in patients with advanced prostate cancer.

METHODOLOGY:

• Studies have reported improved survival with statin use in patients with advanced prostate cancer treated with androgen deprivation therapy (ADT) or androgen receptor pathway inhibitors. However, the relationship between statins and survival among patients on more profound androgen blockades with apalutamide remains unclear.
• Researchers analyzed individual patient data of 2187 participants from two multicenter phase 3 randomized clinical trials, TITAN and SPARTAN. In TITAN, men with metastatic hormone-sensitive prostate cancer were randomly assigned to receive apalutamide or placebo, each given alongside ADT. In SPARTAN, men with nonmetastatic castration-resistant prostate cancer were randomly assigned 2:1 to receive ADT plus apalutamide or ADT plus placebo.
• A total of 1287 patients received apalutamide and 900 received placebo; median ages were 65 years in TITAN and 70 years in SPARTAN. Overall, 748 patients (34.2%; n = 242 in TITAN; n = 506 in SPARTAN) were exposed to statins, defined as use at any point during the assigned treatment period.
• Median follow-up duration for patients with and without statin exposure were 49 and 46 months, respectively.
• OS and cardiac adverse events of grade 3 or higher were the main outcomes.

TAKEAWAY:

• In the overall cohort, statin use was associated with significantly improved OS (hazard ratio [HR], 0.67; 95% CI, 0.48-0.86). Among patients treated with apalutamide, statins were tied to a 42% reduction in the hazard of death (HR, 0.58; 95% CI, 0.42-0.92).
• Statin exposure led to superior OS in patients treated with apalutamide in both TITAN (HR, 0.53; 95% CI, 0.32-0.87) and SPARTAN (HR, 0.54; 95% CI, 0.39-0.74). However, there was no significant association between statin use and OS in the placebo groups of either trial.
• Among patients who received apalutamide, 3-year covariate-adjusted OS rates for patients with vs without statin use were 81% vs 67% in TITAN and 86% vs 78% in SPARTAN.
• Among patients who used statins, 5.8% in the apalutamide cohort and 4.5% in the placebo cohort had a cardiac adverse event of grade 3 or higher. That compared with 2.1% and 1.2%, respectively, among patients with no statin exposure. The difference, the authors note, might reflect pre-existing cardiovascular comorbidity among statin users.

IN PRACTICE:

In this cohort study, “statin exposure during the randomly assigned treatment regimen was associated with a longer overall survival in patients with advanced prostate cancer treated with more profound androgen blockade with apalutamide,” the authors wrote. They stressed, however, that given the exploratory nature of the study, “these findings are at best hypothesis generating, and need further validation in additional studies.” 

SOURCE:

The study, led by Soumyajit Roy, MBBS, MSc, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, Ohio, was published online in JAMA Network Open.

LIMITATIONS:

Limitations included inadequate power to detect between-group differences, risk of false discovery rates, lack of information on serial serum cholesterol levels, residual unmeasured confounding, and residual selection bias. Additionally, the study lacked data on statin dose and duration. Low racial and ethnic minority inclusion limited generalizability.

DISCLOSURES:

The study was supported by the Prostate Cancer Foundation Young Investigator Award. One author was supported by the Hold'em for Life Early Career Professor in Cancer Research, a university limited-term named professorship at the University of Toronto. Several authors reported receiving grants or personal fees and having other ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.