César Serrano1,2, Sebastian Bauer3,4. 1. Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain. cserrano@vhio.net. 2. Sarcoma Translational Research Program, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitario Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035, Barcelona, Spain. cserrano@vhio.net. 3. Department of Medical Oncology, Sarcoma Center, West German Cancer Center, University Duisburg-Essen, Medical School, Essen, Germany. 4. Innere Klinik (Tumorforschung), Universitätsklinikum Essen, Hufelandstraße 55, 45147, Essen, Germany.
Abstract
PURPOSE OF REVIEW: This article critically revisits novel data on tyrosine kinase inhibitors that have shown clinical activity in the treatment of gastrointestinal stromal tumor (GIST). RECENT FINDINGS: GIST therapeutic development exploits the oncogene addiction to KIT or PDGFRA receptor tyrosine kinases. Based on this principle, two new drugs were approved in 2020: ripretinib in GIST patients after progression to all standard treatments and avapritinib, the first agent ever active in the multiresistant PDGFRA D842V-mutant GIST. Additionally, cabozantinib has also shown encouraging activity in imatinib-resistant GIST patients. Finally, novel agents targeting NTRK-driven GIST have emerged as a breakthrough for the treatment of a subset of KIT/PDGFRA wild-type GIST patients. GIST is a paradigmatic tumor model for the rational and successful development of molecularly targeted agents directed against driver mutations in cancer.
PURPOSE OF REVIEW: This article critically revisits novel data on tyrosine kinase inhibitors that have shown clinical activity in the treatment of gastrointestinal stromal tumor (GIST). RECENT FINDINGS: GIST therapeutic development exploits the oncogene addiction to KIT or PDGFRA receptor tyrosine kinases. Based on this principle, two new drugs were approved in 2020: ripretinib in GIST patients after progression to all standard treatments and avapritinib, the first agent ever active in the multiresistant PDGFRA D842V-mutant GIST. Additionally, cabozantinib has also shown encouraging activity in imatinib-resistant GIST patients. Finally, novel agents targeting NTRK-driven GIST have emerged as a breakthrough for the treatment of a subset of KIT/PDGFRA wild-type GIST patients. GIST is a paradigmatic tumor model for the rational and successful development of molecularly targeted agents directed against driver mutations in cancer.
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