2024 Asia Conference on Lung Cancer (ACLC) - Poster & ePosters-PP02.61

PP02.61 - Kin Wong

Pdf Summary

The study investigates the impact of drug dosing on recurrence risk of osimertinib-related QTc prolongation in patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). Osimertinib, a standard treatment, is known to cause QTc prolongation, a risk factor for polymorphic ventricular tachycardia. In a single-center retrospective study involving 970 patients treated with osimertinib from November 2017 to November 2023, 9 (0.9%) developed Grade 3 QTc prolongation, mirroring rates seen in clinical trials.<br /><br />Patients’ electrocardiograms (ECGs) were regularly monitored, and QTc prolongations were categorized according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The study found that baseline QTc prolongation (QTc >450ms) may be a risk factor for developing Grade 3 QTc prolongation. Importantly, no occurrences of ventricular arrhythmia or death related to arrhythmia were reported.<br /><br />Upon encountering Grade 3 QTc prolongation, all nine patients underwent treatment interruption, after which QTc intervals normalized within a median of 15 days. When treatment was rechallenged at 80mg daily, three out of four patients experienced recurrence. A subsequent strategy of dose reduction to 80mg on alternate days or 40mg daily showed reduced recurrence risk, with only one patient having recurrence, managed by further reducing dose to 40mg every three days. Despite these interventions, the median time to treatment failure remained reasonable at 17.7 months.<br /><br />Thus, the study concludes that while the incidence of Grade 3 QTc prolongation is consistent with trials, baseline prolongation may increase risk, and initial rechallenge with osimertinib poses high recurrence, which can be mitigated by dose adjustments. These findings are essential for developing safer treatment strategies for patients at risk of QTc prolongation.

Keywords

osimertinib

QTc prolongation

EGFR mutation-positive

non-small cell lung cancer

ventricular tachycardia

drug dosing

treatment interruption

dose reduction

treatment failure

adverse events