RT Journal Article
T1 Effect of lurbinectedin on the QTc interval in patients with advanced solid tumors: an exposure-response analysis.
A1 Fudio, Salvador
A1 Tabernero, Josep
A1 Subbiah, Vivek
A1 Chawla, Sant P
A1 Moreno, Victor
A1 Longo, Federico
A1 Lopez, Rafael
A1 Anton, Antonio
A1 Trigo, Jose Manuel
A1 Shapiro, Geoffrey
A1 Jeong, Woondong
A1 Villalobos, Victor Manuel
A1 Lubomirov, Rubin
A1 Fernandez-Teruel, Carlos
A1 Alfaro, Vicente
A1 Boni, Valentina
K1 Cardiac repolarization
K1 ECG
K1 Effect compartment
K1 Lurbinectedin
K1 Plasma concentration
K1 QTcF
AB This study assessed the effect of lurbinectedin, a highly selective inhibitor of oncogenic transcription, on the change from baseline in Fridericia's corrected QT interval (∆QTcF) and electrocardiography (ECG) morphological patterns, and lurbinectedin concentration-∆QTcF (C-∆QTcF) relationship, in patients with advanced solid tumors. Patients with QTcF ≤ 500 ms, QRS  A total of 1707 ECGs were collected from 39 patients (females, 22; median age, 56 years). The largest UB of the 90% CI of ΔQTcF was 9.6 ms, thus lower than the more conservative 10 ms threshold established at the ICH E14 guideline for QT studies in healthy volunteers. C-∆QTcF was better fit by an effect compartment model, and the 90% CI of predicted ΔQTcF at Cmax was 7.81 ms, also below the 10 ms threshold of clinical concern. ECG parameters and C-ΔQTcF modelling in this prospective study indicate that lurbinectedin was not associated with a clinically relevant effect on cardiac repolarization.
PB Springer Nature
YR 2020
FD 2020-09-17
LK http://hdl.handle.net/10668/16488
UL http://hdl.handle.net/10668/16488
LA en
NO Fudio S, Tabernero J, Subbiah V, Chawla SP, Moreno V, Longo F, et al. Effect of lurbinectedin on the QTc interval in patients with advanced solid tumors: an exposure-response analysis. Cancer Chemother Pharmacol. 2021 Jan;87(1):113-124
DS RISalud
RD Apr 6, 2025