(P 193) CLINICAL ANALYSIS OF RIPRETINIB DOSE ESCALATION IN ADVANCED GISTS AFTER STANDARD DOSE PROGRESSION

Objective: This study explores the clinical outcomes of ripretinib dose escalation after standard-dose treatment across different treatment lines.

Methods: 16 advanced GIST patients who underwent ripretinib dose escalation after failure of ripretinib standard-dose(150mg qd) were retrospectively analyzed. All patients were treated at the First Affiliated Hospital of Sun Yat-sen University between June 2020 and April 2025. Progression free survival(PFS) was further classified to standard dose(PFS1) and dose escalation (PFS2) phases, respectively.

Results: Primary tumors were from small intestine in 12 patients (75.0%), metastases mainly in the liver (75.0%) and peritoneal cavity (68.6%), with 8 (50.0%) having multi-site metastases. Tumor size (Sum of lesions length diameter) were ≤5 cm in 5 (31.3%), 6-10 cm in 3 (18.8%), and 10-20 cm in 7 (43.8%). Nine (56.3%) received ripretinib as fourth-line treatment; others as second-line (n=3, 18.8%), third-line (n=1, 6.3%), or fifth-line and beyond (n=3, 18.8%). Primary KIT exon 11 mutations were in 12 (75.0%), and 13 (81.3%) had secondary mutations, including 11 (68.8%) with KIT exon 17 mutations and 5 (31.3%) with KIT exon 13 mutations. The median follow-up was 12.3 (2.7-39.0)months. Initial escalated dose was 150 mg bid, with 14 continuing. Two adjusted to 150 mg +100 mg QD/200 mg QD due to adverse reactions. Among three second-line ripretinib patients, no tumor regression was observed and 1 patient(PFS1 21.8m) had tumor progression only in 1.3 months. The other two patient early switched to sunitinib due to lack of response (dose-escalation <=2 months) . The single third-line patient had a PFS1 of 17.8 months, and stable disease for more than 8 months after dose-escalation. Among the 12 fourth-line and beyond patients, the best responses were partial response (PR) in 3 cases, stable disease (SD) in 6 cases, and progressive disease (PD) in 3 cases; the median PFS1 was 3.1 (95% CI: 2.1-8.7) months. After dose escalation, SD was observed in 9 cases and PD in 3 cases; the median PFS2 was 3.3 (95% CI: 2.6-3.5) months. During standard-dose therapy, 11 patients experienced grade 1-2 adverse reactions, and one had grade 3 palmar-plantar erythrodysesthesia. During dose escalation, two developed grade 3 palmar-plantar erythrodysesthesia.

Conclusion: Ripretinib dose escalation may offer additional survival benefits with highly individual diversity. The adverse reactions were tolerable, though patient characteristics predicting benefit require further investigation.