(P061) THE RISK OF QTC PROLONGATION IN PATIENTS USING CYCLIN-DEPENDENT KINASE 4/6 IN ADVANCED BREAST CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS

Background: Cyclin-dependent Kinases 4 and 6 (CDK4/6) inhibitors, combined with endocrine therapy, are the first-line therapy for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Significant adverse events, notably cardiac issues such as QTc interval prolongation, have been observed with these regimens. These events are classified as severe (grade 3) and potentially life-threatening (grade 4) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. This study aims to conduct a meta-analysis to determine whether CDK4/6 inhibitors are associated with QTc prolongation.

METHODS AND RESULTS: We performed a systematic search in PubMed, Cochrane and Embase databases for randomized controlled trials (RCTs) comparing CDK 4/6 to placebo the incidence of QTc prolongation intervals in patients with Breast Cancer HR+/HER2-. We computed for binary endpoints risk ratio (RR) with 95% confidence intervals (CI) were analyzed using a random-effects model. Heterogeneity was assessed using I2 statistics. The statistical analysis was performed using R software, version 4.3.1.
A total of eight RCTs were included; 1183 patients were randomized to CDK 4/6 Inhibitors and 1007 to placebo (either Chemotherapy or endocrinology) and the follow-up period ranging from 8.9 months to 24.5 months, with participant's ages varying from 18 to 92 years old. Analysis of overall of any grades AE showed significant statistically that patients using CDK 4/6 inhibitor, regardless of the specific drug, have a higher risk of QTc interval prolongation (RR: 2.36; 95% CI 1.24 -4.9; p< 0.008; I2: 0%). When comparing overall AE in grade 3/4 of the CDK 4/6 Inhibitors, results showed no statistical significance (RR: 2.21; 95% CI 0,88 - 5.56; p>0.09; I2: 6%). The subgroup analysis revealed that patients using Ribociclib exhibited a higher risk of Qtc interval prolongation (RR: 2.70; 95% CI 1.02- 7.16; p>0,01; I2: 28%) compared to placebo. For the other analysis, there was no significant difference in both Abemaciclib (RR: 1.58; 95% CI 0.10 - 25.08; p=0.74 ) and Palbociclib subgroup (RR: 2.16; 95% CI 0.68 - 6.85; p>0.18; I2: 65%).

Conclusion: This meta-analysis shows the likelihood of QTc interval prolongation with CDK4/6 inhibitors, while also demonstrating their manageable safety profile in severe adverse events. These results reaffirm the efficacy of CDK4/6 inhibitors and underscore their relative safety in treating HR+/HER2- breast cancer, providing crucial insights for clinical decision-making and patient care optimization.