Chylous effusions in advanced medullary thyroid cancer patients treated with selpercatinib

in European Journal of Endocrinology
Authors:
Alessandro Prete Endocrine Unit, Department of Clinical and Experimental Medicine, Pisa University Hospital, Pisa, Italy

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Carla Gambale Endocrine Unit, Department of Clinical and Experimental Medicine, Pisa University Hospital, Pisa, Italy

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Virginia Cappagli Endocrine Unit, Department of Clinical and Experimental Medicine, Pisa University Hospital, Pisa, Italy

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Valeria Bottici Endocrine Unit, Department of Clinical and Experimental Medicine, Pisa University Hospital, Pisa, Italy

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Piercarlo Rossi Diagnostic and Interventional Radiology Unit, Pisa University Hospital, Pisa, Italy

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Marco Caciagli Endocrine Surgery Unit, Department of Surgical, Medical, Molecular Pathology and Critical Area, Pisa University Hospital, Pisa, Italy

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Piermarco Papini Endocrine Surgery Unit, Department of Surgical, Medical, Molecular Pathology and Critical Area, Pisa University Hospital, Pisa, Italy

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Donatella Taddei Chemistry and Endocrinology Laboratory, Pisa University Hospital, Pisa, Italy

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Simona Ortori Diagnostic and Interventional Radiology Unit, Pisa University Hospital, Pisa, Italy

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Luciano Gabbrielli Respiratory Pathophysiology Unit, Department of Surgery, Medicine, Molecular Biology and Critical Care, Pisa University Hospital, Pisa, Italy

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Alessandro Celi Respiratory Pathophysiology Unit, Department of Surgery, Medicine, Molecular Biology and Critical Care, Pisa University Hospital, Pisa, Italy

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Gabriele Materazzi Endocrine Surgery Unit, Department of Surgical, Medical, Molecular Pathology and Critical Area, Pisa University Hospital, Pisa, Italy

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Rossella Elisei Endocrine Unit, Department of Clinical and Experimental Medicine, Pisa University Hospital, Pisa, Italy

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https://orcid.org/0000-0002-5333-9257
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Antonio Matrone Endocrine Unit, Department of Clinical and Experimental Medicine, Pisa University Hospital, Pisa, Italy

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https://orcid.org/0000-0003-4263-4717

Correspondence should be addressed to R Elisei; Email: rossella.elisei@med.unipi.it

*(A Prete and C Gambale contributed equally to this work)

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Objective

Selpercatinib is a highly selective RET-inhibitor drug, approved for the treatment of RET-altered lung and thyroid cancers. So far, RET-altered medullary thyroid cancer (MTC) patients treated with selpercatinib showed a remarkable objective response rate and safety profile. However, new treatment emerging adverse events (TEAEs) have been recently reported. The aim of this study was to evaluate the prevalence, features, and clinical management of effusions that are one of these TEAEs.

Design

Around 10 of 11 patients with advanced MTC enrolled in the LIBRETTO-201 clinical trial at Endocrinology Unit of the Pisa University Hospital were evaluated for the presence and management of effusions.

Methods

We retrospectively evaluated MTC patients treated with selpercatinib. The presence of pleural, pericardial, abdominal, and/or pelvic effusions was evaluated by reviewing the computerized tomography scan performed during the study protocol and up to 24 months of observation.

Results

All but one MTC patient experienced previous multikinase inhibitors treatment. Three patients already had effusions before starting selpercatinib treatment. New effusions appeared in eight of ten (80%) patients during the treatment. A chylous nature was documented in patients who underwent fluid aspiration. Whenever a dose reduction was performed, a significant positive effect was observed.

Conclusions

Chylous effusions are a new TEAE of selpercatinib treatment. They can appear or worsen at any time during the treatment. For cases with asymptomatic and mild effusions, active surveillance may be appropriate and safe. In symptomatic and/or moderate/severe cases, aspiration of the fluid and a dose reduction can improve this AE, strongly supporting a cause-effect correlation with selpercatinib.

Significance statement

Effusions, particularly of chylous nature, represent emergent and quite frequent adverse events in the management of patients affected by advanced MTC on treatment with the highly selective inhibitor selpercatinib. In this study, we evaluated, in a series of MTC patients treated with selpercatinib, the prevalence of pleural, pericardial, abdominal, and/or pelvic effusions. Insights into the diagnosis and treatment of the effusions are provided as well as suggestions for clinical management.

 

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