Effect of lurbinectedin on the QTc interval in patients with advanced solid tumors: an exposure-response analysis.

ABSTRACT:

Purpose

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.

Methods

Patients with QTcF???500 ms, QRS?2 as a 1-h intravenous infusion every 3 weeks. ECGs were collected in triplicate via 12-lead digital recorder in treatment cycle 1 and 2 and analyzed centrally. ECG collection time-matched blood samples were drawn to measure lurbinectedin plasma concentration. No effect on QTc interval was concluded if the upper bound (UB) of the least square (LS) mean two-sided 90% confidence intervals (CI) for ?QTcF at each time point was?ResultsA total of 1707 ECGs were collected from 39 patients (females, 22; median age, 56 years). The largest UB of the 90% CI of ?QTcF 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 ?QTcF at C_max was 7.81 ms, also below the 10 ms threshold of clinical concern.

Conclusions

ECG parameters and C-?QTcF modelling in this prospective study indicate that lurbinectedin was not associated with a clinically relevant effect on cardiac repolarization.

SUBMITTER: Fudio S 

PROVIDER: S-EPMC7801313 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature