NSCLC — SCE Medical Oncology MCQ

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HardLung CancerNSCLCSCE Medical Oncology

A 62-year-old woman with stage IV NSCLC harboring a RET fusion (KIF5B-RET) is identified on NGS. ECOG PS 1. She has not received prior therapy. What is the most appropriate first-line treatment?

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Correct answer: A — Selpercatinib

RET fusions occur in approximately 1-2% of NSCLC. Selpercatinib (NICE TA — LIBRETTO-001/LIBRETTO-431 trials) is a highly selective RET inhibitor demonstrating superior PFS over platinum-pemetrexed ± pembrolizumab as first-line treatment for RET fusion-positive NSCLC. It has excellent CNS activity. Multi-kinase inhibitors (cabozantinib, vandetanib) have off-target RET activity but inferior efficacy and more toxicity compared with selective RET inhibitors.

Reference: ESMO 2024 Metastatic NSCLC Guidelines; LIBRETTO-431 Zhou et al NEJM 2023