Systematic Reviews
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Aug 24, 2024; 15(8): 1092-1101
Published online Aug 24, 2024. doi: 10.5306/wjco.v15.i8.1092
Effect and safety of ripretinib in the treatment of advanced gastrointestinal stromal tumor: A systematic review and meta-analysis
Ji Li, Hao Zhang, Xiao-Dong Chen
Ji Li, Hao Zhang, Xiao-Dong Chen, Department of General Surgery, Chongqing Western Hospital, Chongqing 400051, China
Co-first authors: Ji Li and Hao Zhang.
Author contributions: Li J and Zhang H conceived and designed the study; Chen XD and Zhang H collected data and performed the database search; Li J and Zhang H performed statistical analysis; Li J, Zhang H, Chen XD drafted the manuscript; Li J and Chen XD confirm the authenticity of all the raw data; All authors revised the manuscript; All authors have read and approved the final manuscript.
Conflict-of-interest statement: All authors declare that they have no competing interests.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Dong Chen, MS, Doctor, Master's Student, Department of General Surgery, Chongqing Western Hospital, No. 301 Huafu Road, Jiulongpo, Chongqing 400051, China. 236165437@qq.com
Received: June 23, 2024
Revised: July 18, 2024
Accepted: July 24, 2024
Published online: August 24, 2024
Processing time: 53 Days and 18.6 Hours
Abstract
BACKGROUND

Imatinib (IMA) has received approval as the primary treatment for gastrointestinal stromal tumors (GIST). Nonetheless, approximately half of the patients with advanced GIST show disease advancement following IMA treatment. Presently, the efficacy of secondary and tertiary medications in addressing various GIST secondary mutations is somewhat restricted. Consequently, there is a significant medical demand for the creation of kinase inhibitors that extensively block secondary drug-resistant mutations in advanced GIST. Ripretinib (RPT) is a new, switch-control tyrosine kinase inhibitors that can suppress different mutations of KIT and PDGFRA via a dual mechanism of action.

AIM

To investigate the literature on RPT to assess an effective, safe, and successful treatment strategy against advanced GIST.

METHODS

The present systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Cochrane, Web of Science and ClinicalTrials.gov databases were screened from January 1, 2003 to May 1, 2024.

RESULTS

A total of 4 studies were included, with a total of 507 patients enrolled. The objective response rate (ORR) of the RPT-treated advanced GIST was 17% (95%CI: 0.11-0.27), while the disease control rate (DCR) was 66% (95%CI: 0.59-0.73). The overall occurrence of adverse events with varying degrees was 97% (95%CI: 0.93-1), whereas that of grade ≥ 3 adverse reactions was 42% (95%CI: 0.28-0.63). The sensitivity analysis revealed that omitting some studies did not yield statistically notable variances in the aggregate data regarding the ORR, DCR, and the occurrence of adverse events of grade 3 or higher. The publication bias was absent because no significant asymmetry was observed in Begg’s funnel plot in all studies.

CONCLUSION

RPT has favorable efficacy profiles in GIST patients, but the adverse reactions are obvious, and patient management needs to be strengthened to achieve better safety and tolerability.

Keywords: Gastrointestinal stromal tumor; Ripretinib; PDGFRA; KIT; Meta-analysis

Core Tip: The current therapeutic drugs have limited effectiveness in treating secondary mutations in different gastrointestinal stromal tumor (GIST), and new treatment strategies need to be developed. Ripretinib (RPT) is a new, switch-control tyrosine kinase inhibitors that can suppress different mutations of KIT and PDGFRA via a dual mechanism of action. This study aims to investigate the literature on RPT to assess an effective, safe, and successful treatment strategy against advanced GIST.