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CASE REPORT article
Front. Oncol.
Sec. Thoracic Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1580322
Safety and efficacy of the combination of selpercatinib with osimertinib in NSCLC: a case report and review of the literature
Provisionally accepted- Department of Medicine V, LMU Munich University Hospital, Munich, Bavaria, Germany
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Osimertinib, a 3rd-generation EGFR-TKI (epidermial growth factor receptor-tyrosin chinase inhibitor), has demonstrated significant clinical activity and tolerability in EGFR-positive non- small cell lung cancer (NSCLC) patients. However, acquired resistance to osimertinib is inevitable, and the mechanisms underlying resistance to 3rd-generation EGFR TKIs remain complex and not fully understood. In this case, we report a patient with EGFR-mutated NSCLC who progressed on first-line osimertinib treatment, acquiring an NCOA4-RET (nuclear receptor coactivator 4-rearranged during transfection) fusion alongside a co-mutation in the tumor protein p53 (TP53) gene. Despite these genomic alterations, the patient derived notable clinical benefit from the combination of osimertinib and selpercatinib, suggesting that this dual therapy may offer a promising approach to overcoming resistance in such cases.
Keywords: Non-small cell lung cancer, EGFR, Osimertinib, Selpercatinib, EGFR-TKI acquired resistance
Received: 20 Feb 2025; Accepted: 14 Apr 2025.
Copyright: © 2025 Resuli, Galarza, Oversohl, Kauffmann-Guerrero, Behr and Tufman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Blerina Resuli, Department of Medicine V, LMU Munich University Hospital, Munich, 81377, Bavaria, Germany
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