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. Novel insights Efficacy of selpercatinib in MTC-associated paraneoplastic Cushing’s syndrome. Selpercatinib elicits a rapid and long-lasting response in RET-mutated MTC with bone metastases in the first line. Introduction The
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Established facts Serum CT and CEA are valuable tumour markers in patients with MTC, which most often decrease in parallel after the initiation of efficient treatment. Selpercatinib (LOXO-292) is a highly selective RET kinase
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Highly selective RET inhibitor selpercatinib has demonstrated notable efficacy in advanced/progressive RET-mutant medullary thyroid cancer (MTC) patients. However, despite a more tolerable toxicity profile than multikinase inhibitors, peculiar adverse events (AEs) have been described. Obliterative bronchiolitis (OB) is a respiratory disease characterized by inflammation and fibrosis in small conducting airways. We evaluated a 70 years-old man with advanced RET-mutant MTC who developed OB during treatment with selpercatinib. Radiological features of OB occurred early and persisted during selpercatinib treatment, with a waxing and waning pattern. Notably, a partial response of MTC was achieved during the treatment and selpercatinib was never reduced or interrupted. The almost complete absence of symptoms and the fluctuating trend, without specific treatment for OB, suggested that it is necessary to carefully evaluate the risks mediated by this AE with the risks of modifying or discontinuing the anti-cancer therapy.
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
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Department of Biotechnology and Translational Medicine, University of Milan, Milan, Italy
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Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
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Europe, the multikinase inhibitors sorafenib, lenvatinib (LEN) and cabozantinib have been approved for RAI-R DTC, vandetanib (VAN) and cabozantinib for MTC, and the gene-targeted selpercatinib (SELP) and larotrectinib for cancers harbouring rearranged
Institute of Pathology, University Hospital Halle (Saale), Halle (Saale), Germany
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metastatic, where surgery would result in severe morbidity, or where no satisfactory alternative therapy is available. The receptor tyrosine kinase (RET) inhibitors, selpercatinib and pralsetinib, were approved by the FDA for advanced or metastatic RET
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mutation occurs in codon M918, reported in up to 90% of RET-positive MTC cases ( 2 ). Selpercatinib and pralsetinib, tyrosine-kinase inhibitors with high specificity for RET protein, recently obtained FDA approval for the treatment of lung and thyroid
UMR9019, Genome Integrity and Cancers, CNRS, Villejuif, France
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CHU Nantes/ICO, Saint-Herblain, France
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CHU Nantes/ICO, Saint-Herblain, France
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Université de Paris, Paris, France
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Department of Radiology, AP-HP, Hôpital Cochin, Paris, France
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Department of Nuclear Medicine and Endocrine Oncology, Gustave Roussy Institute, Villejuif, France
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Department of Medical Oncology, AP-HP, Hôpital Cochin, Paris, France
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Université de Paris, Paris, France
Department of Endocrinology, AP-HP, Hôpital Cochin, Paris, France
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performed on brain metastases. The patient was included in a phase 1–2 trial evaluating the highly specific RET inhibitor selpercatinib [ 9 ]. Five weeks after selpercatinib initiation, the patient developed a confusional state. The MRI performed 8 days
College of Medicine, Yonsei University, Seoul, Republic of Korea
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( 26 ). In the open-label, phase 1/2 clinical trial, 20 RET-fusion-positive thyroid cancer patients were included, showing an overall response rate (ORR) of 89% ( 30 ). Wirth et al . reported a comparable response rate in a selpercatinib study, with an
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Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands
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Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
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inhibitors dabrafenib and vemurafenib, MEK inhibitors trametinib and selumetinib, RET inhibitor selpercatinib, and TRK inhibitor larotrectinib) regarding the enhancement of RAI uptake in RAI-refractory NMTC patients. Although these results are promising
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). Recently, this strategy was extended to rarer oncogenic fusion genes like RET and NTRK1/2/3 rearrangements using the RET inhibitor selpercatinib and the NTRK inhibitor larotrectinib ( 6 , 8 , 9 ). The first instance of RAI uptake restoration leading