Avapritinib Response in PDGFRA Exon 18 GIST Management

A 54-year-old female presented to her local primary care with new-onset upper right stomach pain that persisted for a week. The pain was at its worst just after eating and was unrelieved by traditional over-the-counter medications. The patient did not have a significant past medical history, other than obesity with a BMI of 32. Her primary care provider ordered a CT of her abdomen and pelvis, which revealed a large, heterogeneous mass measuring 13.9 x 12.3 x 18.9 cm that appeared to be arising from the anterior retroperitoneal cavity. A percutaneous biopsy was recommended, and the patient was referred to a general surgeon.

Pathology from the endoscopic biopsy came back showing gastric antral mucosa and was negative for malignancy and H. pylori. An endoscopic ultrasound was then completed; cytology was positive for GIST, along with bland epithelioid cells and stromal cells. There was no high-grade nuclear atypia. Immunohistochemistry revealed positivity for CD34.

The patient was then seen by a medical oncologist who requested molecular studies. While the studies were pending, the patient was initiated on imatinib 400 mg daily. A month after the patient started taking imatinib, the report on the molecular studies returned, and a PDGFRA exon 18 missense variant was detected. The medical oncology team met with the patient to discuss switching therapy to avapritinib.

After the patient started on avapritinib, her side effects, which included mild abdominal pain, nausea, and diarrhea, were well-managed with scheduled ondansetron, loperamide, and as-needed ibuprofen. The patient remained on avapritinib for 3 months before a repeat CT of the abdomen and pelvis was repeated. There was a modest decrease in the size of the mass, measuring 10.7 x 10 x 14.5 cm. The decision was made to continue the patient on avapritinib therapy for an additional 3 months, at which time another scan was performed, and the surgical oncology team developed a plan for resection.

Discussion

PDGFRA, or platelet derived growth factor receptor A, mutations drive about 10% of all diagnosed GIST cases.^1-3 Mutations of the PDGFRA gene can be found in exon 18 (approximately 80% of GIST cases), exon 12 (up to 2%), and rarely in exon 14 (<1% of cases).⁴ Those with the PDGFRA D842v mutation are resistant to imatinib.^1,3,5 Avapritinib, a tyrosine kinase inhibitor (TKI), was approved for use after the phase I NAVIGATOR trial, published in 2020, demonstrated the efficacy of the drug against PDGFRA-mutated GISTs and an overall acceptable safety profile.^1,6

The recommended neoadjuvant therapy dose for avapritinib is 300 mg daily.⁷ Adjuvant therapy is not recommended for GISTs with a PDGFRA mutation.¹ Many of the side effects are like those seen with other TKIs, such as nausea, vomiting, abdominal pain, diarrhea, and constipation.^1,3,7 There are some more serious, less common side effects for advanced practice providers to be aware of. These include risk of intracranial hemorrhage, change in cognitive function, and phototoxicity, and may necessitate either a reduction in dose or cessation of the medication entirely.^2,6,7

It is important for the advanced practice provider to effectively communicate with patients when developing an initial plan of care, and to allow the patient to be actively involved in the decision-making process. Building rapport, allowing patients to speak freely without interruption, and providing resources in language that the patient can understand are some ways to do this.³ The NCCN Guidelines are not only written for health-care professionals but are also written in a patient-friendly format.⁸ Prescribing information for medications such as avapritinib are available in patient-friendly brochures, found on the manufacturer’s website.⁷

References:

1. Heinrich MC, Jones RL, von Mehren M, et al. Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase I trial. Lancet Oncol. 2020;21(7):935-946. doi:10.1016/S1470-2045(20)30269-2
2.  Schaefer IM, DeMatteo RP, Serrano C. The GIST of advances in treatment of advanced gastrointestinal stromal tumor. Am Soc Clin Oncol Educ Book. 2022;42:1-15. doi:10.1200/EDBK_351231
3.  Sharkiya SH. Quality communication can improve patient-centred health outcomes among older patients: a rapid review. BMC Health Serv Res. 2023;23(1):886. Published 2023 Aug 22. doi:10.1186/s12913-023-09869-8
4.  Nuñez Hernández I, Gómez Palmero C, Delgado JR, et al. Evaluation of the effectiveness and safety of avapritinib in real-world Spanish cases with gastrointestinal stromal tumor and D842V-PDGFRA Oncologist. 2025;30(5):oyaf062. doi:10.1093/oncolo/oyaf062
5.  Sun Y, Yue L, Xu P, Hu W. An overview of agents and treatments for PDGFRA-mutated gastrointestinal stromal tumors. Front Oncol. 2022;12:927587. Published 2022 Aug 31. doi:10.3389/fonc.2022.927587
6. Casali PG, Blay JY, Abecassis N, et al. Gastrointestinal stromal tumours: ESMO-EURACAN-GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2022;33(1):20-33. doi:10.1016/j.annonc.2021.09.005
7.  Blueprint Medicines. (2025). Ayvakit (Avapritinib). Full prescribing information. https://ayvakit.com/pdgfra-gist/
8. NCCN Guidelines: Gastrointestinal stromal tumors. Version 2.2024; July 31, 2024.