Large-Scale, Multicenter, Prospective Registry Study of Ripretinib in Advanced GIST: A Real-World Study from China.

Abstract

Tyrosine-kinase inhibitors (TKIs) have become the standard treatment for patients with advanced gastrointestinal stromal tumor (GIST); however, secondary mutations can still drive disease progression. Studies have shown that ripretinib, a novel switch-control TKI, inhibits various primary and secondary drug-resistant mutations. There is a paucity of data on the effectiveness and safety of ripretinib in a real-world setting. This prospective, large-scale, real-world registry study aimed to evaluate the effectiveness and safety of ripretinib as a fourth-line treatment in Chinese patients with advanced GIST. Patients≥18years of age having recurrent/metastatic GIST were enrolled. Key endpoints were median progression-free survival (mPFS), median overall survival (mOS), and adverse events (AEs) incidence. Univariate and multivariate analyses were conducted to identify various parameters associated with PFS. A total of 240 patients were enrolled. After a median follow-up period of 6.5months, the mPFS [95% confidence interval (CI)] was 7.70 (6.60, 8.60)months and the mOS was not reached. Multivariate analysis revealed association of Eastern Cooperative Oncology Group (ECOG) performance status score with PFS and superior benefits for non-gastric was observed as compared to gastric GISTs [hazard ratio (HR) 0.58, 95% CI (0.39-0.86)]. Disease control rate and tumor shrinkage (any magnitude) was 73% and 43%, respectively. Ripretinib was also effective in the subgroup of patients with different gene mutations. The toxicities were tolerable, and most reported AEs were alopecia (17.1%) and hand-foot syndrome (15.4%). Ripretinib demonstrated effectiveness and a tolerable safety profile, making it a viable option as a fourth- or later-line treatment in Chinese patients with advanced GISTs, especially for non-gastric GISTs. ClinicalTrials.gov identifier, NCT05697107.