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- Title
Selpercatinib Treatment of RET-Mutated Thyroid Cancers Is Associated With Gastrointestinal Adverse Effects.
- Authors
Tsang, Venessa; Gill, Anthony; Gild, Matti; Lurie, Brett; Blumer, Lucy; Siddall, Rhonda; Clifton-Bligh, Roderick; Robinson, Bruce
- Abstract
Context: Metastatic medullary thyroid carcinoma (MTC) and radioactive iodine–refractory differentiated thyroid carcinoma (RAI-R DTC) have poor prognosis and limited treatment options. Selpercatinib (LOXO-292), a selective kinase inhibitor targeting the RET gene, has shown a 69% to 79% objective response rate in this cohort with benefits in other tumors including lung cancer harboring the same oncogenic driver. Published reports describe only 17% of patients experiencing gastrointestinal (GI) adverse effects (AEs), which is in contrast to our local experience. Objective: Here we characterize the AEs and correlate them with radiological and histopathological findings. Methods: Sequential patients enrolled in LIBRETTO-001 at Royal North Shore Hospital, Sydney, Australia, with available imaging (n = 22) were recruited. Patients had regular visits with AEs documented and computed tomography (CT) scans every 3 months. CT at screening, at time of GI AE, and at most recent follow-up were reviewed and scored. Endoscopic examination was performed in 5 patients. Results: Of 22 patients in this cohort, the majority had somatic RET alterations (n = 18), most commonly p.Met918Thr (n = 14). Ten patients (50%) developed GI AEs. Dose reduction was required in 8 of the 10 patients, but none discontinued therapy. The majority had stable disease (n = 17). Gastric and small-bowel edema was evident in symptomatic patients after a median time of 67 weeks’ treatment. Histological correlation in 5 patients revealed mucosal edema correlating with radiological evidence of congestion and edema. Conclusion: GI AEs with selpercatinib may be more common than previously described. Most are self-limiting but often require dose adjustments. Histological evidence of mucosal edema observed in conjunction with the radiological findings of congestion and wall thickening suggest bowel-wall edema is a predominant mechanism of abdominal pain in these patients.
- Subjects
THYROID cancer; GASTROINTESTINAL agents; HISTOPATHOLOGY
- Publication
Journal of Clinical Endocrinology & Metabolism, 2022, Vol 107, Issue 9, pe3824
- ISSN
0021-972X
- Publication type
Article
- DOI
10.1210/clinem/dgac337