Introduction: Ribociclib, a cyclin-dependent kinase 4/6 inhibitor, has improved survival in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER 2)-negative advanced breast cancer. Despite remarkable efficacy, potential cardiac toxicities remain a concern. We undertook a combined analysis of randomized controlled trials (RCT) to estimate the incidence of prolongation of corrected QT interval (QTcF) associated with ribociclib. Methods: We performed systematic search of Embase, MEDLINE, and meeting abstracts till September 30, 2018, to find all phase 3 RCTs comparing ribociclib with other agents or placebo in patients with advanced breast cancer and reporting QTc prolongation as adverse event. Mantel-Haenszel method was used to calculate the pooled risk ratio (RR) and absolute risk difference (RD) with 95% CI. Fixed effects model was applied. Heterogeneity was assessed using I2 statistic. Results: Three phase III studies with 2,062 participants were included. Randomization ratio was 1 to 1 in MONALEESA-2 and 7 studies and 2 to 1 in MONALEESA-3 study. I2 statistic was 0, suggesting homogeneity across studies. Prolongation of QTcF >60 msec from baseline was observed in 72 patients (61 had post-baseline QTcF >480 msec) in ribociclib arm, compared to 7 in control arm. Pooled RR for prolongation of QTcF was 7.956 (95%CI: 3.683–17.187; P<.001) and RD was 0.055 (95%CI: 0.040–0.070; P<.001). The risk of having a post-baseline QTcF >480 msec was significantly higher with ribociclib vs control (pooled RR, 4.002; 95%CI: 2.161–7.412; P<.001; and RD, 0.039; 95%CI: 0.024–0.055; P<.001). A total of 16 (1.38%) patients in the ribociclib arm had dose reduction, interruption, or discontinuation due to QTcF prolongation, as opposed to 3 (0.33%) in control arm. Pooled RR and RD were statistically significant at 4.204 (95%CI: 1.333–3.260; P=.014) and 0.012 (95%CI: 0.004–0.021; P=.006), respectively. Conclusion: Advanced breast cancer patients may have cardiac dysfunction due to prior cardiotoxic chemotherapies. In our meta-analysis, ribociclib was associated with significantly higher risk of QTc prolongation and the resultant dosing inconsistencies and discontinuation. Early detection of this potential adverse event and timely intervention are critical.
PCN207 COST COMPARISON OF ADVERSE EVENT MANAGEMENT WITH POLY(ADP-RIBOSE) POLYMERASE (PARP) INHIBITORS OR CHEMOTHERAPY IN GBRCA-MUTATED, HER2-NEGATIVE ADVANCED BREAST CANCER (ABC): A US AND GERMAN HEALTHCARE PERSPECTIVE
