NSCLC — SCE Medical Oncology MCQ

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HardLung CancerNSCLCSCE Medical Oncology

A 48-year-old non-smoker with metastatic NSCLC has an HER2 (ERBB2) exon 20 insertion mutation identified on NGS. EGFR/ALK/ROS1 wild-type. She progresses on first-line immunochemotherapy. What targeted therapy has emerging evidence in this setting?

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Correct answer: D — Trastuzumab deruxtecan

HER2 mutations (distinct from HER2 amplification) occur in approximately 2-3% of NSCLC, predominantly exon 20 insertions. Trastuzumab deruxtecan (T-DXd) has demonstrated significant activity in HER2-mutant NSCLC (DESTINY-Lung02 trial, response rate approximately 49%). NICE appraisal is pending. T-DXd is an ADC, distinct from traditional anti-HER2 approaches (trastuzumab/pertuzumab) which have limited activity in HER2-mutant NSCLC.

Reference: ESMO 2024 Metastatic NSCLC Guidelines; DESTINY-Lung02 Goto et al JCO 2023