Molekulare Diagnostik und Therapie des Differenzierten Schilddrüsenkarzinoms

Zusammenfassung

Zusammenfassend ergeben sich somit eine Vielzahl an Therapiemöglichkeiten für radiojodrefraktäre differenzierte Schilddrüsenkarzinome ([Abb. 1]). Primär kann durch eine gezielte Redifferenzierungstherapie eine erneute Radiojodtherapie ermöglicht werden. Des Weiteren stehen mit Sorafenib und Lenvatinib in der Erstlinie der medikamentösen Systemtherapien 2 effektive VEGFR-Inhibitoren zur Verfügung. Lenvatinib wird hierbei als wirksamer angesehen. Bei Versagen von Sorafenib ist der Wechsel auf den noch breiter wirksamen VEGFR/FGFR-Inhibitor Lenvatinib sinnvoll. Bei Progress auf Lenvatinib ist eine molekulare Diagnostik mittels frischer Biopsie notwendig, um spezifische, medikamentös angehbare Läsionen wie BRAF-V600E-, RET- und NTRK-Fusionen zu identifizieren und mittels spezifischer Inhibitoren zu blockieren. Bei Fehlen spezifischer Treibermutationen stehen als Salvage-Therapien Cabozantinib oder die Hinzunahme eines Immuncheckpoint-Inhibitors zur Verfügung.

Abstract

In summary, there are thus a variety of therapeutic options for radioiodine-refractory differentiated thyroid carcinomas ([Abb. 1]). Primarily, a targeted redifferentiation therapy can enable a renewed radioiodine therapy. Furthermore, with sorafenib and lenvatinib, 2 effective VEGFR inhibitors are available in the first line of drug system therapies. Lenvatinib is considered to be more effective. If sorafenib fails, switching to the even more broadly effective VEGFR/FGFR inhibitor lenvatinib makes sense. In case of progression on lenvatinib, molecular diagnostics by means of fresh biopsy is necessary to identify specific, drug-targeted lesions such as BRAF-V600E, RET and NTRK fusions and to block them with specific inhibitors. In the absence of specific driver mutations, salvage therapies include cabozantinib or the addition of an immune checkpoint. addition of an immune checkpoint inhibitor. are available.

Kernaussagen

• 15–20 % der differenzierten Schilddrüsenkarzinome benötigen im Laufe der Erkrankung eine Systemtherapie.

• Klassische Chemotherapien und eine externe Strahlentherapie sind beim radiojodrefraktären Schilddrüsenkarzinom kaum wirksam.

• In der Erstlinie werden breit wirksame Neoangiogenese-Inhibitoren wie Lenvatinib und Sorafenib eingesetzt.

• Bei Versagen ist eine gezielte molekulare Diagnostik auf BRAF-Mutationen sowie RET- und NTRK-Fusionen notwendig.

• Für die Zweitliniensystemtherapie können nach Krankenkassenantrag spezifische Inhibitoren gegen BRAF, RET oder NTRK eingesetzt werden.

• Alternativ, bei fehlenden spezifischen Mutationen, kann eine Behandlung mit Cabozantinib (zugelassen) oder Immuncheckpoint-Inhibitoren (Krankenkassenantrag) erfolgen.

Schlüsselwörter

Schilddrüsenkarzinom - DTC - Immuntherapie - molekulare Diagnostik - Kinaseinhibitor - VEGFR-Inhibitor - VEGFR/FGFR - Immuncheckpoint-Inhibitor

Keywords

Thyroid carcinomas - VEGFR inhibitor - VEGFR/FGFR - immune checkpoint inhibitor

Publication History

Article published online:
28 August 2023

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