Navigating Treatment Challenges in Metastatic Gastric Gastrointestinal Stromal Tumor (GIST): A Case Report of Sequential Four-Line Targeted Therapy and Palliative Transition in a Resource-Limited Setting

Gastrointestinal stromal tumors (GISTs) represent the primary mesenchymal neoplasms of the gastrointestinal tract and are driven predominantly by oncogenic gain-of-function mutations in KIT or platelet-derived growth factor receptor alpha.Although small-molecule tyrosine kinase inhibitors (TKIs) have transformed the management of advanced disease, administering multiple lines of systemic therapy, managing secondary drug resistance, controlling toxicities, and navigating drug supply chain disruptions in low-and middle-income countries present complex clinical challenges.Here, we present the case of a 55year-old man who presented with a large primary gastric fundic GIST and synchronous bilobar liver metastases.Diagnostic core needle biopsy confirmed a spindle cell GIST demonstrating positivity for CD117 and CD34, a Ki-67 proliferation index of approximately 2%, and negativity for pan-cytokeratin.Over a threeyear clinical course, the patient received four sequential lines of TKI therapy: frontline imatinib mesylate, 400 mg orally daily; second-line sunitinib malate, 37.5 mg orally daily on a modified two-week on and twoweek off schedule.Sunitinib treatment was associated with a reduction in the reported tumor diameter from 13.3 cm to 7.6 cm (approximately 42.9%), based on the available imaging measurements; third-line regorafenib, 160 mg orally daily, administered three weeks on and one week off, which was complicated by severe drug-induced hypothyroidism, with a thyroid-stimulating hormone level of 25.34 mIU/L, for which levothyroxine replacement was initiated; and fourth-line ripretinib, 150 mg orally daily, following progression during regorafenib treatment.Subsequent radiological disease progression, worsening anemia, lower extremity edema secondary to hypoalbuminemia, drug supply interruptions, and a lack of clinical benefit after the third cycle of ripretinib led to a timely transition to best supportive palliative care.Multiline management of GISTs in resource-limited settings requires serial cross-sectional CT monitoring, individualized TKI treatment modifications in response to toxicity, and a timely transition to palliative care when further treatment provides no meaningful clinical benefit.