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      Dramatic clinical response to dabrafenib plus trametinib in anaplastic thyroid carcinoma and the challenges faced during the COVID-19 pandemic

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          SUMMARY

          Anaplastic thyroid carcinoma is the rarest tumor of the thyroid gland, representing less than 2% of clinically recognized thyroid cancers. Typically, it has an extremely rapid onset, fatal outcomes in most cases, and a median overall survival of 3 to 10 months despite aggressive multidisciplinary management. The presence of targetable mutations in anaplastic thyroid carcinoma patients is an opportunity for treatment when conventional therapeutics approaches are not effective, a frequent situation in the majority of patients. We present our experience in the management of a patient with unresectable anaplastic thyroid cancer who had a remarkable and rapid response to treatment with dabrafenib and trametinib during the COVID-19 pandemic. After four weeks of dabrafenib 150 mg twice daily plus trametinib 2 mg daily, he showed a dramatic reduction of the cervical mass around 90%. Nearly eight weeks under treatment with dabrafenib plus trametinib, the patient remains with minimal locoregional disease without distant metastases.

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          Most cited references36

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          Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials

          Background The selective TRK inhibitor larotrectinib was approved for paediatric and adult patients with advanced TRK fusion-positive solid tumours based on a primary analysis set of 55 patients. The aim of our analysis was to explore the efficacy and long-term safety of larotrectinib in a larger population of patients with TRK fusion-positive solid tumours. Methods Patients were enrolled and treated in a phase 1 adult, a phase 1/2 paediatric, or a phase 2 adolescent and adult trial. Some eligibility criteria differed between these studies. For this pooled analysis, eligible patients were aged 1 month or older, with a locally advanced or metastatic non-CNS primary, TRK fusion-positive solid tumour, who had received standard therapy previously if available. This analysis set includes the 55 patients on which approval of larotrectinib was based. Larotrectinib was administered orally (capsule or liquid formulation), on a continuous 28-day schedule, to adults mostly at a dose of 100 mg twice daily, and to paediatric patients mostly at a dose of 100 mg/m 2 (maximum of 100 mg) twice daily. The primary endpoint was objective response as assessed by local investigators in an intention-to-treat analysis. Contributing trials are registered with ClinicalTrials.gov , NCT02122913 (active not recruiting), NCT02637687 (recruiting), and NCT02576431 (recruiting). Findings Between May 1, 2014, and Feb 19, 2019, 159 patients with TRK fusion-positive cancer were enrolled and treated with larotrectinib. Ages ranged from less than 1 month to 84 years. The proportion of patients with an objective response according to investigator assessment was 121 (79%, 95% CI 72–85) of 153 evaluable patients, with 24 (16%) having complete responses. In a safety population of 260 patients treated regardless of TRK fusion status, the most common grade 3 or 4 larotrectinib-related adverse events were increased alanine aminotransferase (eight [3%] of 260 patients), anaemia (six, 2%), and decreased neutrophil count (five [2%]). The most common larotrectinib-related serious adverse events were increased alanine aminotransferase (two [<1%] of 260 patients), increased aspartate aminotransferase (two [<1%]), and nausea (two [<1%]). No treatment-related deaths occurred. Interpretation These data confirm that TRK fusions define a unique molecular subgroup of advanced solid tumours for which larotrectinib is highly active. Safety data indicate that long-term administration of larotrectinib is feasible. Funding Bayer and Loxo Oncology.
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            Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers.

            Poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) are rare and frequently lethal tumors that so far have not been subjected to comprehensive genetic characterization.
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              Efficacy of Selpercatinib in RET-Altered Thyroid Cancers

              RET mutations occur in 70% of medullary thyroid cancers, and RET fusions occur rarely in other thyroid cancers. In patients with RET-altered thyroid cancers, the efficacy and safety of selective RET inhibition are unknown.
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                Author and article information

                Journal
                Arch Endocrinol Metab
                Arch Endocrinol Metab
                aem
                Archives of Endocrinology and Metabolism
                Sociedade Brasileira de Endocrinologia e Metabologia
                2359-3997
                2359-4292
                15 February 2021
                Mar-Apr 2021
                : 65
                : 2
                : 242-247
                Affiliations
                [1 ] orgnameUniversity of Buenos Aires orgdiv1Division of Endocrinology Buenos Aires Argentina originalDivision of Endocrinology, University of Buenos Aires, Buenos Aires, Argentina
                [2 ] orgnameUniversity of Buenos Aires orgdiv1Department of Pathology Buenos Aires Argentina originalDepartment of Pathology, University of Buenos Aires, Buenos Aires, Argentina
                Author notes
                Correspondence to: Fabián Pitoia, Division of Endocrinology, University of Buenos Aires, Córdoba 2351, C 1120 Buenos Aires, Argentina fpitoia@ 123456intramed.net

                Disclosure: no potential conflict of interest relevant to this article was reported.

                Author information
                https://orcid.org/0000-0001-9333-4576
                https://orcid.org/0000-0001-5217-3294
                https://orcid.org/0000-0002-9629-8459
                https://orcid.org/0000-0001-7190-6182
                https://orcid.org/0000-0002-2742-7085
                Article
                2359-3997000000325
                10.20945/2359-3997000000325
                10065318
                33587835
                28a293b4-513c-404b-b6a7-ee99391f467f

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 September 2020
                : 02 December 2020
                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 30
                Categories
                Case Report

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