(P 101) CYTOREDUCTIVE SURGERY FOR METASTATIC GASTROINTESTINAL STROMAL TUMORS TREATED WITH RIPRETINIB: A SINGLE-CENTER ANALYSIS.

Objective: The standard treatment for advanced gastrointestinal stromal tumor (GIST) is tyrosine kinase inhibitors (TKIs) therapy. Outcome of patients who become resistant to imatinib is poor. Surgery demonstrated a significant improvement in survival benefits in selected patient groups. Ripretinib (RIP) is the fourth-line standard treatment with a relatively high objective response rate (ORR) and good tolerance that may provide surgical opportunities for patients resistant to imatinib. However, surgery after RIP treatment has seldom been reported. This study aims to introduce a single-center experience of RIP treatment and performing surgery after RIP treatment on patients with advanced GISTs.

Methods: Of 34 patients diagnosed with advanced GIST and treated with RIP, 7 underwent surgery after RIP treatment. All cases were collected in our hospital between January 2020 to June 2022. The preoperative treatment, clinicopathological characteristics, and surgical information were collected.

Results: In total, 34 patients were given RIP, as 2nd, 3rd, and >=4th line therapy in 11.7%, 17.6%, and 70.6% of patients, respectively. Seven (20.7%) patients with metastatic GIST underwent cytoreductive surgery after RIP treatment. R0/1 resection was performed in 6 (85.7%), and 1 (14.3%) was of R2 resection. All patients underwent at least 1 surgery on GIST before. All 7 patients developed secondary mutation before RIP treatment, 2 (28.6%) in KIT exon 11+13, 5 (71.4%) in KIT exon 11+17/18. RIP was applied as the 2nd and >=4th line therapy in 3 and 4 patients. The median time of pre-op RIP treatment was 66 (range 31-153) days. Drug withdrawal was at 3-13 (median 5) days before surgery. Five were at the standard dose (150 mg once daily), 1 at a high dose (150 mg twice daily) after disease progression (PD), and 1 reduced to 100 mg/d. Grade 1-2 adverse events (AEs) were observed in 85.71% of patients. Two (28.6%) reported grade 3 AEs: hand-foot syndrome, and leukopenia, respectively. The best therapeutic effect was partial response (PR) in 1 (14.3%), stable disease (SD) in 5 (71.4%), and PD in 1 (14.3%) of the patients. The tumors reduced by 7.0%-32.3% in the sum of diameter of targeted lesions in 5 patients. The final therapeutic effect before surgery was SD in 4 patients, while PD in the rest (42.8%) with a median time-to-progression of 59.5 (range 27-86) days. Six patients underwent open surgery and 1 had laparoscopic surgery. The median time of surgery was 400 (range 225-734) minutes. The mean volume of blood loss was 450.14 (range 30-4000; median 800) ml. The median post-op days was 8 (range 4-34) days. Two (28.6%) patients had post-op complications: one with gastric paralysis (IId), the other with intestinal fistula (IId), according to the Clavien-Dindo classification. Postoperative outcome was closely related to the preoperative RIP response. All 4 patients with SD before surgery remain non-evidence of disease in a median follow-up of 3.7 (range 0.7-17.0) months.

Conclusion: According to our study, RIP has a favorable safety profile and demonstrated substantial promising efficacy in advanced GIST. RIP treatment may create a chance for feasible cytoreductive surgery in carefully selected patients. Further prospective clinical research on the therapeutic effects of surgery and RIP treatment with better patient selection is necessary.