(P 164) CLINICAL BENEFITS OF RIPRETINIB AND CYTOREDUCTIVE SURGERY IN IMATINIB-RESISTANT ADVANCED GASTROINTESTINAL STROMAL TUMORS (GISTS): A RETROSPECTIVE DUAL-CENTER STUDY

Objective: Advanced GIST patients may derive survival benefits from cytoreductive surgery under the conditions, such as response to TKI therapy, localized progression, or acute abdominal symptoms like intestinal obstruction. Ripretinib, as a switch control tyrosine kinase inhibitor, has demonstrated a high objective response rate and an acceptable safety profile, potentially creating opportunities for cytoreductive surgery. This study aims to evaluate the efficacy and safety of cytoreductive surgery during ripretinib treatment in advanced GIST patients who have progressed on imatinib.

Methods: Patients with recurrent or metastatic GIST who received ripretinib from October 19, 2020, to May 27, 2024, at Zhejiang Cancer Hospital and the First Affiliated Hospital of Wenzhou Medical University were enrolled. The clinical characteristics and treatment information of all patients were collected. In addition, the perioperative information for patients who underwent cytoreductive surgery during ripretinib treatment was retrospectively collected. The clinical efficacy and safety were analyzed.

Results: A total of 42 patients treated with ripretinib were included, with a median age of 59 years. The small intestine was the primary tumor site in 67.4%, and liver metastases were observed in 51.2% of the cases. Ripretinib was administered as second-, third-, and fourth-line treatment in 32.6%, 25.6%, and 41.9% of the cohort, yielding objective response rate (ORR) of 21.4%, 18.2%, and 11.8%, respectively, along with an overall ORR of 16.7% for the entire patients. After a median follow-up of 14.3 months, the median progression-free survival (PFS) for each treatment line was not reached (NR), 17.4 months, and 11.0 months, without any new safety signals. Eleven patients underwent cytoreductive surgery following a median of 4.3 months on ripretinib. Indications for surgery included stable disease in 3 cases, acute abdomen in 5, and localized progression in 3. The best responses to preoperative ripretinib were PR in 2 and SD in 9 cases. Surgery was preceded after a 7-day preoperative treatment interruption. Surgical approaches included open surgery in 8 and laparoscopy in 3 cases, achieving R0, R1, and R2 resection statuses in 4, 2, and 5 cases, respectively. Perioperative complications occurred in 4 patients, including 2 anastomotic leaks, 1 paralytic ileus and 1 CVC (Central Venous Catheter) infection, without any mortality. Nine patients resumed ripretinib postoperatively. With a median follow-up of 8.8 months, the median postoperative PFS was not reached. A suggestive trend towards the mPFS benefit was observed in the surgery group, pending longer-term follow-up for definitive mPFS data.

Conclusion: Ripretinib demonstrates promising efficacy and safety in treating imatinib-resistant advanced GIST patients. The integration of cytoreductive surgery with ripretinib therapy may offer select patients additional clinical benefits. The emerging trend of improved PFS with the combined approach indicates a need for further research to confirm these preliminary findings.