Rare subdural hematoma in a patient treated with avapritinib for gastrointestinal stromal tumor: A case report

Abstract

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal malignancy of the digestive tract, accounting for 1% of all digestive tract malignancies. GISTs occur most frequently in the stomach, followed by the small intestine and colorectum, and rarely in the mesentery, omentum, and retroperitoneum. Avapritinib’s approval for GISTs in 2020 marks a milestone in precision oncology, showing its significant antitumor activity against the resistant platelet-derived growth factor receptor-alpha D842V mutation. It has a manageable safety profile, with dose adjustments for mitigating side effects without reducing efficacy. Avapritinib-induced subdural hematomas are rare but potentially lethal complications. Our patient had a metastatic small bowel GIST and liver metastases and began avapritinib treatment in January 2024. He had a stable condition until early May. He presented with acute encephalopathy, altered mentation, and left subdural hematoma, which was suspected to be caused by avapritinib, resulting in its discontinuation. Despite receiving diligent care, the patient’s condition did not improve, and he eventually died.

Keywords

Gastrointestinal stromal tumors / Chemotherapeutics / Novel targets / Side effects / Subdural hematomas

Funding

None.

Conflict of interest

Syed A. A. Rizvi is an Editorial Board Member of this journal but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.

References

[1] Suresh Babu MC, Chaudhuri T, Babu KG, et al. Metastatic gastrointestinal stromal tumor: A regional cancer center experience of 44 cases. South Asian J Cancer. 2017; 6(3):118-121. doi: 10.4103/sajc.sajc_290_16

[2] Ahmed M. Recent advances in the management of gastrointestinal stromal tumor. World J Clin Cases. 2020; 8(15):3142-3155. doi: 10.12998/wjcc.v8.i15.3142

[3] Teuber A, Schulz T, Fletcher BS, et al. Avapritinib-based SAR studies unveil a binding pocket in KIT and PDGFRA. Nat Commun. 2024; 15(1):63. doi: 10.1038/s41467-023-44376-8

[4] Vallilas C, Sarantis P, Kyriazoglou A, et al. Gastrointestinal stromal tumors (GISTs): Novel therapeutic strategies with immunotherapy and small molecules. Int J Mol Sci. 2021; 22(2):493. doi: 10.3390/ijms22020493

[5] Cao L, Tian W, Zhao Y, et al. Gene mutations in gastrointestinal stromal tumors: Advances in treatment and mechanism research. Glob Med Genet. 2024; 11(4):251-262. doi: 10.1055/s-0044-1789204

[6] Jones RL, Serrano C, von Mehren M, et al. Avapritinib in unresectable or metastatic PDGFRA D842V-mutant gastrointestinal stromal tumours: Long-term efficacy and safety data from the NAVIGATOR phase I trial. Eur J Cancer. 2021; 145:132-142. doi: 10.1016/j.ejca.2020.12.008

[7] Zhang H, Liu Q. Prognostic indicators for gastrointestinal stromal tumors: A review. Transl Oncol. 2020; 13(10):100812. doi: 10.1016/j.tranon.2020.100812

[8] Reiter A, Schwaab J, DeAngelo DJ, et al. Efficacy and safety of Avapritinib in previously treated patients with advanced systemic mastocytosis. Blood Adv. 2022; 6(21):5750-5762. doi: 10.1182/bloodadvances.2022007539

[9] Joseph CP, Abaricia SN, Angelis MA, et al. Optimal avapritinib treatment strategies for patients with metastatic or unresectable gastrointestinal stromal tumors. Oncologist. 2021; 26(4):e622-e631. doi: 10.1002/onco.13632

[10] George S, Jones RL, Bauer S, et al. Avapritinib in patients with advanced gastrointestinal stromal tumors following at least three prior lines of therapy. Oncologist. 2021; 26(4):e639-e649. doi: 10.1002/onco.13674

[11] Li J, Zhang X, Deng Y, et al. Efficacy and safety of avapritinib in treating unresectable or metastatic gastrointestinal stromal tumors: A phase I/II, open-label, multicenter study. Oncologist. 2023 ;28(2):187-e114. doi: 10.1093/oncolo/oyac242

[12] Gotlib J, Castells M, Elberink HO, et al. Avapritinib versus placebo in indolent systemic mastocytosis. NEJM Evid. 2023; 2(6):EVIDoa2200339. doi: 10.1056/EVIDoa2200339

[13] Hossain M, Habib I, Singha K, Kumar A. FDA-approved heterocyclic molecules for cancer treatment: Synthesis, dosage, mechanism of action and their adverse effect. Heliyon. 2023; 10(1):e23172. doi: 10.1016/j.heliyon.2023.e23172

[14] Rong L, Xie M, Jiang M, Qiu H, Kong L. A post-marketing pharmacovigilance study of Avapritinib: Adverse event data mining and analysis based on the United States Food and drug administration adverse event reporting system database. Br J Clin Pharmacol. 2024; 90(8):1816-1826. doi: 10.1111/bcp.15673