Update 2020: Systemische Therapie des differenzierten und medullären Schilddrüsenkarzinoms

Zusammenfassung

Für das fortgeschrittene Radiojod-refraktäre differenzierte Schilddrüsenkarzinom (DTC) als auch für das progrediente medulläre Schilddrüsenkarzinom sind seit mehreren Jahren Tyrosinkinase-Inhibitoren (TKI) als wirksame Therapieoptionen zugelassen. Nicht zuletzt aufgrund des Toxizitätsprofiles der TKIs erfolgt deren Einsatz individualisiert und risikoadaptiert nach Ausschöpfen lokaler palliativer Therapieverfahren und wenn bei großer Tumormasse und/oder signifikantem Fortschreiten ein weiteres Abwarten nicht mehr vertretbar erscheint. Für das DTC gibt es zwei zugelassene Tyrosinkinaseinhibitoren, Lenvatinib und Sorafenib; für das MTC sind es ebenfalls zwei, Vandetanib und Cabozantinib. Hinzu kommen, vor allem in letzter Zeit, (relativ) selektive Inhibitoren einzelner Tyrosinkinasen (z. B. BRAF, MEK, NTRK, RET und mTOR), die im Rahmen von Studien oder im individuellen Heilversuch zur Verfügung stehen. Kürzlich erlangten zwei NTRK-Inhibitoren die europäische Zulassung und können bei Vorliegen einer NTRK-Fusion eingesetzt werden; leider ist diese Fusion jedoch relativ selten beim Schilddrüsenkarzinom zu finden.

In Summe sind die Nebenwirkungen der selektiven Inhibitoren meist geringer als die der bisher zugelassenen Medikamente, bei teils besserer, teils gleicher und teils etwas schlechterer Wirkung. Es steht zu erwarten, dass die selektiven Inhibitoren zukünftig das therapeutische Spektrum ergänzen werden. Grundvoraussetzung ist jedoch eine molekulare Analyse von Tumorgewebe mit Nachweis einer spezifischen Veränderung im Sinne eines „drugable target“. Um eine optimale individuelle Therapieplanung unter Berücksichtigung aller möglichen Therapieoptionen, inklusive Einschluss in klinische Studien, zu gewährleisten, sollten Patienten mit fortgeschrittenem MTC oder Radiojod-refraktären DTC interdisziplinär an spezialisierten Zentren (mit-)betreut werden.

Abstract

Since several years, tyrosine kinase inhibitors (TKI) have been approved as effective therapy options for advanced radiojodine-refractory differentiated thyroid carcinoma (DTC) and for progressive medullary thyroid carcinoma. Not only because of the toxicity profile of the TKIs, their use should be applied individualized and risk-adapted after exhausting local palliative therapy procedures and if, in the case of large tumor mass and/or significant progression, it is no longer justifiable to wait and watch. There are two approved tyrosine kinase inhibitors for DTC, lenvatinib and sorafenib; there are also two for MTC, vandetanib and cabozantinib. In addition, recently, there have been (relatively) selective inhibitors of individual tyrosine kinases (e. g. BRAF, MEK, NTRK, RET and mTOR) introduced, which are available in studies or in compassionate use programs. Two NTRK inhibitors have recently received European approval and can be used if there is an NTRK fusion; unfortunately, this fusion is relatively rare in thyroid cancer.

In general, the side effects of the selective inhibitors are usually less than those of the previously approved TKIs, with partly better, partly comparable and partly little poorer effect. It is expected that the selective inhibitors will complement the therapeutic spectrum in the future. The basic requirement, however, is a molecular analysis of tumor tissue with evidence of a specific mutation in the sense of a „drugable target“. In order to ensure optimal individual therapy planning considering all possible therapy options, including inclusion in clinical studies, patients with advanced MTC or radiojodine-refractory DTC should be (inter) disciplinarily discussed at specialized centers.

Schlüsselwörter

Tyrosinkinaseinhibitor - systemische Therapie - selektiver Inhibitor - differenziertes Schilddrüsenkarzinom - medulläres Schilddrüsenkarzinom

Keywords

Tyrosinkinaseinhibitor - systemic therapy - selective inhibitor - differentiated thyroid cancer - medullary thyroid cancer

Publication History

Article published online:
21 September 2020

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