11537 Background: Cytoreductive surgery may improve outcomes in patients with locally advanced or metastatic gastrointestinal stromal tumors (GIST) after progression on imatinib. Ripretinib has shown a high objective response rate (ORR) and a favorable safety profile in advanced GIST, suggesting its potential for tumor downstaging and enabling surgical intervention. This study evaluated the efficacy and safety of ripretinib as preoperative therapy in patients with imatinib-resistant, potentially resectable advanced GIST. Methods: This single-arm, multicenter, exploratory study (NCT05132738) enrolled patients with imatinib-resistant, locally advanced or recurrent metastatic GIST who met the following criteria: 1) ≤5 evaluable lesions on CT/MRI; 2) resection deemed high-risk by multidisciplinary team (MDT) assessment (meeting one of the following): a) The maximum diameter of a single lesion is ≥10 cm; b) Organ function damage surgery is required; c) Multiple organ resection surgery is required. Patients received ripretinib 150 mg once daily (QD) up to 6 months before surgery. The primary endpoint was the no evidence of disease rate (NED Rate). Secondary endpoints included the R0/R1 resection rate, surgery rate, and ORR. Results: As of January 2026, 20 patients were enrolled, with a median age of 58 years (range: 31-74). The most common primary tumor site was the small intestine (70%). The median sum of target lesion diameters was 10.8 cm (range: 3.2-33.7). The median duration of preoperative ripretinib was 5 months (range: 2-6). The median best percentage change in the sum of target lesion diameters was -20.5% (range: -47.2% to +56.0%). 8 patients (40.0%) achieved a partial response (PR) and 10 patients (50.0%) had stable disease (SD). Median time to response was 2.0 months (range: 2.0-6.0). 70% (14/20) of patients underwent surgery and the NED rate was 92.9% (13/14). Of the 13 patients who achieved R0 resection, 8 (61.5%) have maintained NED to date. Only 1 patient experienced intestinal fistula as a surgical complication, which was unrelated to ripretinib treatment. After surgery, 6 patients continued ripretinib therapy, while 3 switched to imatinib therapy and 5 switched to sunitinib therapy. With a median follow-up of 20.4 months (range: 8.1–47.6), the median overall survival (OS) was immature. Conclusions: These findings demonstrate that preoperative ripretinib effectively reduced tumor burden in patients with imatinib-resistant, potentially resectable advanced GIST, and facilitated successful surgery intervention. Notably, the approach achieved a high NED rate and a low surgical complication rate, supporting ripretinib as a safe and effective preoperative treatment option. Clinical trial information: NCT05132738 .
Yang et al. (Wed,) studied this question.