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Original article: Central nervous system disease in patients with RET fusion-positive non-small cell lung cancer treated with selpercatinib

Open AccessPublished:January 16, 2023DOI:https://doi.org/10.1016/j.jtho.2023.01.008
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      ABSTRACT

      Background

      Central nervous system (CNS) metastases develop in nearly half of patients and cause morbidity and mortality in RET fusion-positive non-small cell lung cancers (NSCLCs). The selective RET inhibitor selpercatinib treats existing intracranial disease, but no studies have investigated whether early initiation of selpercatinib is associated with decreased development of CNS metastases.

      Patients and methods

      Sixty-one patients with RET fusion-positive advanced NSCLC with and without CNS metastases treated with selpercatinib on the LIBRETTO-001 trial (NCT03157128) or the LIBRETTO-201 expanded access program (EAP, NCT03906331) were identified. Cumulative incidence rates (CIRs) for CNS metastases were assessed as an event-of-interest; systemic progression of disease and death were considered competing risks.

      Results

      The median age was 65 years, and the most common 5’ fusion partners were KIF5B (67%) and CCDC6 (18%). Twenty-four patients (39%) received prior platinum chemotherapy; twenty patients (33%) received prior multikinase inhibition. The median time on selpercatinib was 21.8 months. Thirty patients (49%) had CNS disease at baseline, and thirty-one patients (51%) had no baseline CNS disease. CIRs of CNS progression among patients with baseline CNS disease were 3% (95% CI: 0-10%), 10% (95% CI: 0-22%), 17% (3-30%), 17% (3-30%), and 20% (5-35%) at 6, 12, 18, 24, and 36 months, respectively. CIRs for CNS progression among patients without baseline CNS disease were 0% at 6, 12, 18, 24, and 36 months (95% CI: 0-0%).

      Conclusions

      CNS progression was not observed with selpercatinib therapy in patients without baseline CNS disease. CNS progression on selpercatinib was rare in patients with baseline CNS disease. Early initiation of selpercatinib is associated with decreased rates of CNS metastasis formation and progression, and may play a preventive role.

      Keywords