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Imatinib und darüber hinaus – was ist wichtig für die Chirurgie?

Imatinib and beyond—what is important for surgery?

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Zusammenfassung

Die Behandlung gastrointestinaler Strumatumoren (GIST) ist seit Einführung von KIT-Inhibitoren dramatisch verbessert worden. Eine Heilung gelingt allerdings unverändert nur auf der Grundlage einer operativen Therapie des Primärtumors. Auch in der metastasierten Situation erscheint die Chance auf eine langfristige Tumorkontrolle durch Tyrosinkinaseinhibitoren (TKI) nach dem Erreichen einer ggf. chirurgischen kompletten Resektion höher zu sein. Die Entscheidung, welche Patienten am ehesten von multimodalen Konzepten profitieren, basiert inzwischen neben klinischen Faktoren auch auf einer Vielzahl molekularer Prädiktoren und verlangt eine Besprechung in multidisziplinären, erfahrenen Behandlungsteams. Neue, breiter wirksame Inhibitoren ermöglichen ein Therapieansprechen auch bei bislang refraktären GIST-Subtypen wie den PDGFR-D842V-mutierten GIST, aber scheinen auch bei KIT-mutierten GIST nach dem Versagen aller zugelassenen Therapien einen therapeutischen Nutzen aufzuweisen. Hier ist eine grundlegende Änderung der Behandlungssequenzen in naher Zukunft zu erwarten.

Abstract

The treatment of gastrointestinal stromal tumors (GIST) has dramatically improved since the introduction of small molecule KIT proto-oncogene receptor tyrosine kinase inhibitors. Nevertheless, the cure of patients is still based on surgical treatment of the primary tumor. The chance of long-term tumor control by tyrosine kinase inhibitors (TKI) even in the metastatic setting also appears to be improved after achieving a surgical complete resection. The decision on which patients will most likely profit from multimodal treatment approaches is increasingly based on complex molecular predictors in addition to clinical factors and also a profound understanding of the biology of GIST that requires discussion in a multidisciplinary, highly experienced treatment team. Novel, more potent inhibitors enable a response to treatment in so far treatment-refractory GIST subtypes, such as the platelet-derived growth factor receptor (PDGFR) D842V mutated GIST subtype and also appear to show treatment benefits even in KIT mutated GIST after the failure of all approved treatments. These treatments are expected to profoundly change treatment algorithms in the near future.

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Abbreviations

BRAF:

Homolog B, rapidly accelerated fibrosarcoma (serine/threonine-protein kinase)

EMA:

European Medicines Agency (Europäische Arzneimittel-Agentur)

GIST:

Gastrointestinaler Stromatumor

HPF:

High-power-field

KIT:

Proto-oncogene tyrosine-protein kinase Kit (c-kit), CD117, mast/stem cell growth factor receptor precursor (SCFR)

NTRK:

Neurotrophic tyrosine kinase

PDGFRA:

Platelet-derived growth factor receptor A

SDH:

Succinat-Dehydrogenase

TKI:

Tyrosinkinaseinhibitoren

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Authors and Affiliations

  1. Innere Klinik (Tumorforschung), Sarkomzentrum am Westdeutschen Tumorzentrum, Universitätsklinik Essen, Universität Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Deutschland

    R. Hamacher,  J. Falkenhorst &  S. Bauer

  2. Sektion Viszerale/retroperitoneale Sarkome und GIST, Klinik für Allgemein‑, Viszeral- und Transplantationschirurgie, Sarkomzentrum am Westdeutschen Tumorzentrum, Universitätsklinik Essen, Universität Duisburg-Essen, Essen, Deutschland

    J. Treckmann

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Correspondence to S. Bauer.

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Interessenkonflikt

R. Hamacher: Novartis (Einladung zu Kongressteilnahme). S. Bauer: Advisory Role: Blueprint Medicines, ADC Therapeutics, Lilly, Novartis, Daichii, Lilly, Plexxikon, Nanobiotix, Deciphera; CME Honoraria: Novartis, Pfizer, Bayer, Lilly, Pharmamar; Research Support: Blueprint Medicines, Incyte, Novartis. J. Falkenhorst und J. Treckmann geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Hamacher, R., Falkenhorst, J., Treckmann, J. et al. Imatinib und darüber hinaus – was ist wichtig für die Chirurgie?. Chirurg 90, 462–469 (2019). https://doi.org/10.1007/s00104-019-0934-0

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