An open-label study to investigate the cardiac safety profile of cabazitaxel in patients with advanced solid tumors.
OBJECTIVE
This 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.


METHODS
Patients with advanced solid tumors were treated with cabazitaxel 25 mg/m(2) 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.


RESULTS
The 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.


CONCLUSIONS
These results suggest that cabazitaxel has no clinically significant cardiovascular adverse effects in patients with advanced solid tumors.
Cardiology Unit, Assistance Publique des Hôpitaux de Paris, Hôpital Bichat, Paris, France, ipmb@wanadoo.fr.
Pierre
P
Maison-Blanche
Shaker
S
Dakhil
Ari
A
Baron
Sylvie
S
Rottey
Fred
F
Millard
Gedske
G
Daugaard
Jean-Pascal
JP
Machiels
William
W
Conkright
Sunil
S
Sharma
Patricia M M B
PM
Soetekouw
Jeffrey
J
Yachnin
Lisa
L
Sengeløv
Peter
P
Van Veldhuizen
Sanjiv S
SS
Agarwala
Dorothée
D
Sémiond
Mustapha
M
Chadjaa
Liji
L
Shen
James L
JL
Wade
D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011446:Prospective Studies; D043823:Taxoids / Q000009:adverse effects* / Q000627:therapeutic use*
D043823:Taxoids; C552428:cabazitaxel