The BRAF Status May Predict Response to Sorafenib in Gastrointestinal Stromal Tumors Resistant to Imatinib, Sunitinib, and Regorafenib: Case Series and Review of the Literature

Caspar Franck; Rosa Rosania; Sabine Franke; Johannes Haybaeck; Ali Canbay; Marino Venerito

doi:10.1159/000490886

The BRAF Status May Predict Response to Sorafenib in Gastrointestinal Stromal Tumors Resistant to Imatinib, Sunitinib, and Regorafenib: Case Series and Review of the Literature

Digestion. 2019;99(2):179-184. doi: 10.1159/000490886. Epub 2018 Sep 4.

Authors

Caspar Franck¹, Rosa Rosania¹, Sabine Franke², Johannes Haybaeck², Ali Canbay¹, Marino Venerito³

Affiliations

¹ Department of Gastroenterology, Hepatology and Infectious Diseases, Magdeburg, Germany.
² Department of Pathology, Otto-von-Guericke University Hospital, Magdeburg, Germany.
³ Department of Gastroenterology, Hepatology and Infectious Diseases, Magdeburg, [email protected].

PMID: 30179868
DOI: 10.1159/000490886

Abstract

Background: Sorafenib has shown efficacy in patients with imatinib-, sunitinib-, and regorafenib-resistant gastrointestinal stromal tumors (GISTs). No biomarker is currently available for predicting response to sorafenib in patients with GIST.

Methods: We herein report 3 patients with imatinib-, sunitinib-, and regorafenib-resistant metastasized GISTs, who were treated with sorafenib. Besides receptor tyrosine kinase KIT and platelet-derived growth factor receptor α, also BRAF was tested for mutations.

Results: Sorafenib therapy induced a long-term disease control in 2 out of 3 patients over a period of 49 and 19 months, respectively. Sorafenib-responsive GISTs were BRAF wild-type, whereas the sorafenib-resistant GIST carried a BRAF V600E mutation.

Conclusion: We confirm sorafenib as an effective therapeutic option in patients with imatinib-, sunitinib-, and regorafenib-resistant GISTs. Larger studies are required to corroborate whether BRAF mutation may predict sorafenib resistance in GISTs.

Keywords: BRAF mutation; Gastrointestinal stromal tumor; Sorafenib.

Publication types

Case Reports
Review

MeSH terms

Antineoplastic Agents / pharmacology*
Antineoplastic Agents / therapeutic use
Chemotherapy, Adjuvant / methods
Drug Resistance, Neoplasm / drug effects
Drug Resistance, Neoplasm / genetics
Drug Substitution
Gastrointestinal Neoplasms / genetics
Gastrointestinal Neoplasms / pathology
Gastrointestinal Neoplasms / therapy*
Gastrointestinal Stromal Tumors / genetics
Gastrointestinal Stromal Tumors / pathology
Gastrointestinal Stromal Tumors / therapy*
Humans
Imatinib Mesylate / pharmacology
Imatinib Mesylate / therapeutic use
Male
Middle Aged
Mutation
Phenylurea Compounds / pharmacology
Phenylurea Compounds / therapeutic use
Protein Kinase Inhibitors / pharmacology*
Protein Kinase Inhibitors / therapeutic use
Proto-Oncogene Proteins B-raf / antagonists & inhibitors
Proto-Oncogene Proteins B-raf / genetics*
Pyridines / pharmacology
Pyridines / therapeutic use
Sorafenib / pharmacology*
Sorafenib / therapeutic use
Sunitinib / pharmacology
Sunitinib / therapeutic use
Treatment Outcome

Substances

Antineoplastic Agents
Phenylurea Compounds
Protein Kinase Inhibitors
Pyridines
regorafenib
Imatinib Mesylate
Sorafenib
BRAF protein, human
Proto-Oncogene Proteins B-raf
Sunitinib