Addition of Trastuzumab Deruxtecan to Selpercatinib in a Patient With RET Fusion-Driven NSCLC and an Acquired HER2 Amplification: Case Report

Despite the high activity of selective RET inhibitors in RET-driven NSCLC, resistance eventually develops and there is unmet need to better define therapeutic options for pa-tients. This is a case of a patient initially thought to have no targetable alterations, then found to have a RET fusion, and subsequently HER2 amplification on three distinct bi-opsies. She was treated initially with chemotherapy and immune therapy, then switched to selpercatinib, and eventually had fam-trastuzumab deruxtecan added to sel-percatinib. She also developed neuroendocrine differenti-ation at time of progression in the context of a p53 mutation, which is a known factor that can lead to small cell transformation. This patient's case highlights the need for comprehensive molecular testing at both diagnosis and progression, as unexpected resistance mechanisms may be identified particularly for patients with uncommon driver mutations.(c) 2023 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).