Chylous effusions in advanced medullary thyroid cancer patients treated with selpercatinib

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

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

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

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

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Piercarlo RossiDiagnostic and Interventional Radiology Unit, Pisa University Hospital, Pisa, Italy

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

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

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Donatella TaddeiChemistry and Endocrinology Laboratory, Pisa University Hospital, Pisa, Italy

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Simona OrtoriDiagnostic and Interventional Radiology Unit, Pisa University Hospital, Pisa, Italy

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

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

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

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Rossella EliseiEndocrine 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 MatroneEndocrine 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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  • 1

    Bradford D, Larkins E, Mushti SL, Rodriguez L, Skinner AM, Helms WS, Price LSL, Zirkelbach JF, Li Y & Liu J et al.FDA approval summary: selpercatinib for the treatment of lung and thyroid cancers with RET gene mutations or fusions. Clinical Cancer Research 2021 27 21302135. (https://doi.org/10.1158/1078-0432.CCR-20-3558)

    • Search Google Scholar
    • Export Citation
  • 2

    Della Corte CM, Morgillo F. Rethinking treatment for RET-altered lung and thyroid cancers: selpercatinib approval by the EMA. ESMO Open 2021 6 100041. (https://doi.org/10.1016/j.esmoop.2020.100041)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Matrone A, Gambale C, Prete A, Elisei R. Sporadic medullary thyroid carcinoma: Towards a precision medicine. Frontiers in Endocrinology (Lausanne) 2022 13 864253. (https://doi.org/10.3389/fendo.2022.864253)

    • Search Google Scholar
    • Export Citation
  • 4

    European Medicines Agency 2021. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/retsevmo.

  • 5

    Wirth LJ, Sherman E, Robinson B, Solomon B, Kang H, Lorch J, Worden F, Brose M, Patel J & Leboulleux S et al.Efficacy of selpercatinib in RET-altered thyroid cancers. New England Journal of Medicine 2020 383 825835. (https://doi.org/10.1056/NEJMoa2005651)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S & Mooney M et al.. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). European Journal of Cancer version 1.1 2009 45 228247. (https://doi.org/10.1016/j.ejca.2008.10.026)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Kalchiem-Dekel O, Falcon CJ, Bestvina CM, Liu D, Kaplanis LA, Wilhelm C, Eichholz J, Harada G, Wirth LJ & Digumarthy SR et al.Brief report: chylothorax and chylous ascites During RET tyrosine kinase inhibitor therapy. Journal of Thoracic Oncology 2022 17 11301136. (https://doi.org/10.1016/j.jtho.2022.06.008)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Bhardwaj R, Vaziri H, Gautam A, Ballesteros E, Karimeddini D, Wu GY. Chylous ascites: a review of pathogenesis, diagnosis and treatment. Journal of Clinical and Translational Hepatology 2018 6 105113. (https://doi.org/10.14218/JCTH.2017.00035)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Center for Transportation Engineering and Planning CTEP. Common Terminology Criteria for Adverse Events (CTCAE), v.5.0 [5x7] Cancer Therapy Evaluation Program. 2017. Available at: http://ctep.cancer.gov/

    • Search Google Scholar
    • Export Citation
  • 10

    Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. American Journal of Clinical Oncology 1982 5 649655. (https://doi.org/10.1097/00000421-198212000-00014)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Tuttle M, Morris L, Haugen B, Shah J, Sosa J, Rohren E, Subramaniam R, Hunt J, Perrier N & Amin M et al.Thyroid-Differentiated and Anaplastic Carcinoma (Chapter 73). New York, NY: Springer International Publishing 2017.

    • Search Google Scholar
    • Export Citation
  • 12

    Huggins JT Chylothorax and cholesterol pleural effusion. Seminars in Respiratory and Critical Care Medicine 2010 31 743750. (https://doi.org/10.1055/s-0030-1269834)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Subbiah V, Hu MI, Wirth LJ, Schuler M, Mansfield AS, Curigliano G, Brose MS, Zhu VW, Leboulleux S & Bowles DW et al.Pralsetinib for patients with advanced or metastatic RET-altered thyroid cancer (ARROW): a multi-cohort, open-label, registrational, phase 1/2 study. Lancet. Diabetes and Endocrinology 2021 9 491501. (https://doi.org/10.1016/S2213-8587(2100120-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Tsang V, Gill A, Gild M, Lurie B, Blumer L, Siddall R, Clifton-Bligh R, Robinson B. Selpercatinib treatment of RET mutated thyroid cancers is associated with gastrointestinal adverse effects. Journal of Clinical Endocrinology and Metabolism 2022 107 e3824e3829. (https://doi.org/10.1210/clinem/dgac337)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    McGrath EE, Blades Z, Anderson PB. Chylothorax: aetiology, diagnosis and therapeutic options. Respiratory Medicine 2010 104 18. (https://doi.org/10.1016/j.rmed.2009.08.010)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Koylu B, Tekin F, Aktas BY, Kilickap S, Koksal D. Pazopanib-induced chylothorax in a patient with renal cell carcinoma. Anti-Cancer Drugs 2022 33 e555e557. (https://doi.org/10.1097/CAD.0000000000001172)

    • Search Google Scholar
    • Export Citation
  • 17

    Chen B, Wu Z, Wang Q, Li W, Cheng D. Dasatinib-induced chylothorax: report of a case and review of the literature. Investigational New Drugs 2020 38 16271632. (https://doi.org/10.1007/s10637-020-00932-3)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Phan C, Jutant EM, Tu L, Thuillet R, Seferian A, Montani D, Huertas A, Bezu JV, Breijer F & Vonk Noordegraaf A et al.Dasatinib increases endothelial permeability leading to pleural effusion. European Respiratory Journal 2018 51. (https://doi.org/10.1183/13993003.01096-2017)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Takahashi M RET receptor signaling: function in development, metabolic disease, and cancer. Proceedings of the Japan Academy. Series B, Physical and Biological Sciences 2022 98 112125. (https://doi.org/10.2183/pjab.98.008)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Williams SP, Odell AF, Karnezis T, Farnsworth RH, Gould CM, Li J, Paquet-Fifield S, Harris NC, Walter A & Gregory JL et al.Genome-wide functional analysis reveals central signaling regulators of lymphatic endothelial cell migration and remodeling. Science Signaling 2017 10. (https://doi.org/10.1126/scisignal.aal2987)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Giani C, Valerio L, Bongiovanni A, Durante C, Grani G, Ibrahim T, Mariotti S, Massa M, Pani F & Pellegriti G et al.Safety and quality-of-life data from an Italian expanded access program of lenvatinib for treatment of thyroid cancer. Thyroid 2021 31 224232. (https://doi.org/10.1089/thy.2020.0276)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Locati LD, Piovesan A, Durante C, Bregni M, Castagna MG, Zovato S, Giusti M, Ibrahim T, Puxeddu E & Fedele G et al.Real-world efficacy and safety of lenvatinib: data from a compassionate use in the treatment of radioactive iodine-refractory differentiated thyroid cancer patients in Italy. European Journal of Cancer 2019 118 3540. (https://doi.org/10.1016/j.ejca.2019.05.031)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Valerio L, Bottici V, Matrone A, Piaggi P, Viola D, Cappagli V, Agate L, Molinaro E, Ciampi R & Tacito A et al.Medullary thyroid cancer treated with vandetanib: predictors of a longer and durable response. Endocrine-Related Cancer 2020 27 97110. (https://doi.org/10.1530/ERC-19-0259)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Cappagli V, Moriconi D, Bonadio AG, Giannese D, La Manna G, Egidi MF, Comai G, Vischini G, Bottici V & Elisei R et al.Proteinuria is a late-onset adverse event in patients treated with cabozantinib. Journal of Endocrinological Investigation 2021 44 95103. (https://doi.org/10.1007/s40618-020-01272-y)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Kalchiem-Dekel O, Falcon CJ, Bestvina CM, Liu D, Kaplanis LA, Wilhelm C, Eichholz J, Harada G, Wirth LJ & Lee RP et al.Chylothorax and chylous ascites during RET tyrosine kinase inhibitor therapy. Journal of Clinical Oncology 2022 40 90809080. (https://doi.org/10.1200/JCO.2022.40.16_suppl.9080)

    • Search Google Scholar
    • Export Citation
  • 26

    Wells SA Jr, Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M, Baudin E, Elisei R, Jarzab B & Vasselli JR et al.Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. Journal of Clinical Oncology 2012 30 134141. (https://doi.org/10.1200/JCO.2011.35.5040)

    • Search Google Scholar
    • Export Citation