[Efficacy and safety analysis of neoadjuvant avapritinib in patients with platelet-derived growth factor receptor α D842V-mutant gastrointestinal stromal tumors].

Objective: To evaluate the efficacy of avapritinib as neoadjuvant therapy in gastrointestinal stromal tumor (GIST) with platelet-derived growth factor receptor α (PDGFRA)- D842V mutation. Methods: We conducted a retrospective analysis of patients with gastrointestinal stromal tumors harboring the PDGFRA-D842V mutation who received neoadjuvant treatment with avapritinib. Clinical and pathological data were retrieved from 7 medical institutions [Union Hospital of Tongji Medical College, Huazhong University of Science and Technology (3 cases); Fudan University Shanghai Cancer Center (3 cases); Peking University Cancer Hospital & Institute (2 cases); Peking University People's Hospital (1 case); Sun Yat-sen University Cancer Center (1 case); the First Affiliated Hospital of Chongqing Medical University (1 case); the Affiliated Hospital of Qingdao University (1 case)] from October 2019 to March 2025, including the patients' demographic data, laboratory and imaging findings, neoadjuvant therapy history, operative details, pathologic and genetic testing results, as well as postoperative adjuvant treatment and follow-up information. Results: After excluding 1 patient with concomitant gastric cancer, 7 patients presenting with distant metastasis at initial diagnosis or a prior history of GIST surgery, and 2 patients with incomplete clinical data, a total of 12 patients with PDGFRA-D842V mutations who received avapritinib neoadjuvant therapy were enrolled in this study. There were 8 male patients and 4 female patients, with a mean age at diagnosis of (56.0±12.4) years. Among them, 5 cases received a dosage of 300 mg/day, 2 cases received 200 mg/day, 2 cases received 150 mg/day, and 3 cases received 100 mg/day. The maximum tumor diameter before and after neoadjuvant therapy was (15.7±4.9) cm vs. (10.1±4.1) cm, respectively (t=5.998, P < 0.001), and the median time to best response was 4.5 (3.3,5.0) months. Among the 12 patients, 9 achieved partial response and 3 achieved stable disease, yielding an overall disease control rate of 100%. Common adverse events included anemia (8 cases), elevated bilirubin (6 cases), periorbital edema (5 cases), leukopenia (4 cases), and decreased neutrophil count (4 cases). Grade ≥3 adverse events occurred in eight patients, primarily anemia (2 cases), elevated bilirubin (2 cases), and leukopenia (1 case). All these adverse events resolved following appropriate supportive management. After achieving maximal response to neoadjuvant therapy, all 12 patients underwent surgical resection with curative intent. The median operative time was 95.0 (82.5, 120.0) minutes, and the median intraoperative blood loss was 50.0 (20.0, 175.0) ml. Among them, 7 patients underwent laparoscopic surgery, and 5 underwent open surgery. A total of 2 patients in the entire cohort underwent combined organ resection, including partial hepatectomy and partial transverse colectomy. The median postoperative length of hospital stay was 8.0 (7.0, 9.8) days, and no Clavien-Dindo grade III or higher complications occurred. Postoperatively, 5 patients continued treatment with avapritinib. The median follow-up duration was 20.5 (15.3, 37.3) months. The 2-year disease-free survival and overall survival rates were 68.2% and 77.9%, respectively. Conclusions: Avapritinib as neoadjuvant therapy in patients with PDGFRA-D842V-mutant gastrointestinal stromal tumors demonstrates significant efficacy in reducing tumor size and improving the rate of complete resection. Despite a relatively high incidence of adverse events, the treatment exhibits a manageable safety profile and is generally well tolerated.