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

Abstract

Introduction 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. Methods Patients ≥ 18 years 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. Results A total of 240 patients were enrolled. After a median follow-up period of 6.5 months, 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%). Conclusion 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. Trial Registration ClinicalTrials.gov identifier, NCT05697107. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-023-02576-0.

Efficacy and Safety of Ripretinib in Advanced Gastrointestinal Stromal Tumors within an Expanded Access Program: A Cohort Study

“…Our study supports the role of EAPs as a means to gather early real-world evidence on the safety and efficacy of drugs, including ripretinib [ 20 , 21 ], outside of clinical trials. It confirms treatment with ripretinib as an effective strategy for patients with advanced GIST in the UK.…”