Abstract P5-14-22: QT-interval prolongation during the treatment with ribociclib and endocrine agents in patients with hormone receptor-positive, human epidermal growth factor 2-negative metastatic breast cancer: A real-world experience

Abstract

Abstract Objective: In hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) metastatic breast cancer (MBC), endocrine therapy (Tx) combined with an inhibitor of cycline-dependent kinases 4/6 (CDK4/6i) has now widely been accepted as the new standard-of-care in the first- and second-line setting. Among different agents available, the CDK4/6i ribociclib (RIBO) has been documented to be able to prolong cardiac repolarization as measured by the corrected QT interval (QTc). Cardiac monitoring by consecutive echocardiograms (ECGs) is thus recommended in MBC patients (pts) while being on RIBO treatment. However, little is known about the incidence and severity of QTc prolongation during RIBO therapy which should thus be further analyzed in the present investigation. Methods: A total of 29 pts were included, 7 pts were premenopausal and 22 were postmenopausal. All premenopausal pts underwent ovarian suppression with goserelin (ZOL). Endocrine treatment consisted of letrozole (LET) in 23 pts, exemestane (EXE) in 1 pt and fulvestrant (FULV) in 5 pts. In all pts, QTc was measured at start of RIBO and thereafter every 2-4 weeks (wks) for a maximum of 262 days while being on treatment. Mean QTc values were calculated at baseline (BL) and at 6 consecutive time points: #1 (d7-21 from BL), #2 (22-42d from BL), #3 (d43-63 from BL), #4 (d64-84 from BL), #5 (d85-105 from BL), #6 (d105-126 from BL). Changes of mean QTc values were analyzed with repeated measure ANOVA with p≤0.05 indicating statistical significance. Results: QTc showed a slight but not significant increase during RIBO Tx (p=0.306) with a maximum at #3. Whenever observed, QTc prolongation did not exceed 110% from BL in all but 4 pts. In the latter, QTc returned to normal values in all but 1 pt. OTc exceeding 480 ms were not observed at any time of the observation time. At BL, 17 pts had a normal ECG whereas 9 pts had preexisting ECG abnormalities other than long QT syndrome. 3 pts with normal ECG at BL developed ECG abnormalities during Tx with RIBO. No patient experienced a significant deterioration of cardiac ejection fraction while being on Tx. Conclusion: Clinically meaningful QTc prolongations did not occur in this real-world population of MBC pts treated with RIBO and endocrine agents. Moreover, cardiac function did not deteriorate during RIBO Tx neither in patients with normal ECG nor in those with (preexisting or newly diagnosed) ECG abnormalities. QTc prolongations induced by RIBO may thus be of minor importance in the clinical routine and the necessity of intensive ECG monitoring in pts subjected to RIBO is thus a matter of debate. Citation Format: Christian M Kurbacher, Alexander Schott, Ann T Kurbacher, Susanne Herz, Lotta A Fischer, Jutta A Kurbacher, Mathias Warm. QT-interval prolongation during the treatment with ribociclib and endocrine agents in patients with hormone receptor-positive, human epidermal growth factor 2-negative metastatic breast cancer: A real-world experience [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-22.