Central nervous system effectiveness of selpercatinib retreatment in heavily pretreated NSCLC patient with RET rearrangement: A case report

Introduction: RET-rearranged non-small cell lung cancer (NSCLC) is a rare molecular subtype, accounting for 1-2% of all lung cancers. Selpercatinib, a selective RET tyrosine kinase inhibitor (TKI), has demonstrated efficacy in this oncogene-addicted population, but data on rechallenge after disease progression are lacking. Case description: A 70-year-old male was diagnosed with a metastatic RET-positive adenocarcinoma of the lung. At the time of systemic progressive disease on first-line chemo-immunotherapy, he received selpercatinib for 22 months before further central nervous system (CNS) progression. After whole-brain radiotherapy and third-line chemotherapy, selpercatinib was resumed due to further CNS progression and lack of other therapeutic options. Remarkably, the patient achieved an almost complete CNS remission. Conclusion: This case suggests that selpercatinib rechallenge may be effective in difficult-to-treat RET-positive NSCLC patients, including those with uncontrolled CNS disease.