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An open-label study to investigate the cardiac safety profile of cabazitaxel in patients with advanced solid tumors |
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| Authors: | Pierre Maison-Blanche Shaker Dakhil Ari Baron Sylvie Rottey Fred Millard Gedske Daugaard Jean-Pascal Machiels William Conkright Sunil Sharma Patricia M. M. B. Soetekouw Jeffrey Yachnin Lisa Sengeløv Peter Van Veldhuizen Sanjiv S. Agarwala Dorothée Sémiond Mustapha Chadjaa Liji Shen James L. Wade |
| Affiliation: | 1. Cardiology Unit, Assistance Publique des H?pitaux de Paris, H?pital Bichat, Paris, France 2. Cancer Center of Kansas, Wichita, KS, USA 3. California Pacific Medical Center, San Francisco, CA, USA 4. Ghent University Hospital, Ghent, Belgium 5. Moores UCSD Cancer Center, La Jolla, CA, USA 6. Rigshospitalet, Copenhagen, Denmark 7. Department of Medical Oncology, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (Pole MIRO), Université Catholique de Louvain, Brussels, Belgium 8. Purchase Cancer Group, Paducah, KY, USA 9. Huntsman Cancer Institute, Salt Lake City, UT, USA 10. Division of Medical Oncology, Maastricht University Medical Center, Maastricht, The Netherlands 11. University Hospital Uppsala, Uppsala, Sweden 12. Department of Oncology, Herlev Hospital, Herlev, Denmark 13. Kansas City Veterans Administration Medical Center, Kansas City, MO, USA 14. St Luke’s Cancer Center and Temple University, Bethlehem, PA, USA 15. Sanofi, Paris, France 16. Sanofi, Bridgewater, NJ, USA 17. Clinical Research, Decatur Memorial Hospital, Decatur, IL, USA |
| Abstract: | PurposeThis study assessed the cardiovascular safety of cabazitaxel, based on thorough evaluation of QT and non-QT variables, and the relationship between pharmacokinetic and pharmacodynamic electrocardiographic (ECG) profiles and the occurrence of Grade ≥3 cardiovascular adverse events.MethodsPatients with advanced solid tumors were treated with cabazitaxel 25 mg/m2 every 3 weeks. Digital ECG recordings were obtained during Cycle 1 over 24 h after dosing. The primary end point was effect of cabazitaxel on QT interval corrected by the Fridericia formula (QTcF). Secondary end points were additional ECG parameters (QT, PR and QRS intervals, and heart rate), plasma pharmacokinetics of cabazitaxel and overall clinical safety.ResultsThe pharmacodynamic (ECG) population included 94 patients. In 63 patients with a full 24-h ECG evaluation, the maximum upper bound of 90 % confidence interval (CI) for mean QTcF change from baseline was 7.46 ms (mean 4.8 ms), occurring at 1 h 30 min post-infusion. The slope of QTcF change from baseline versus cabazitaxel concentration was slightly negative (?0.012 [95 % CI ?0.017; ?0.008], equivalent to a 1.2 ms decrease per 100 ng/mL increase in cabazitaxel concentration). For non-QT variables, no effect was noted. No Grade ≥3 cardiac adverse events were observed; Grade ≥3 hypotension and lymphocele occurred in two patients and one patient, respectively.ConclusionThese results suggest that cabazitaxel has no clinically significant cardiovascular adverse effects in patients with advanced solid tumors. |
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