%0 Journal Article
%A Fudio, Salvador
%A Tabernero, Josep
%A Subbiah, Vivek
%A Chawla, Sant P
%A Moreno, Victor
%A Longo, Federico
%A Lopez, Rafael
%A Anton, Antonio
%A Trigo, Jose Manuel
%A Shapiro, Geoffrey
%A Jeong, Woondong
%A Villalobos, Victor Manuel
%A Lubomirov, Rubin
%A Fernandez-Teruel, Carlos
%A Alfaro, Vicente
%A Boni, Valentina
%T Effect of lurbinectedin on the QTc interval in patients with advanced solid tumors: an exposure-response analysis.
%D 2020
%U http://hdl.handle.net/10668/16488
%X 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.
%K Cardiac repolarization
%K ECG
%K Effect compartment
%K Lurbinectedin
%K Plasma concentration
%K QTcF
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