Efficacy of post-first-line agents for advanced gastrointestinal stromal tumors following imatinib failure: A network meta-analysis.

Abstract

BACKGROUND:

Imatinib is the standard first-line treatment for advanced gastrointestinal stromal tumors (GISTs); however, most patients eventually develop imatinib resistance, leading to considerable clinical challenges. Few direct comparisons have been made between different post-first-line therapies on clinical efficacy in advanced GIST following imatinib failure.

METHODS:

Databases including PubMed, Embase, Scopus, Google Scholars, and Cochrane Library from inception to February 2023 were retrieved for randomized controlled trials evaluating the clinical efficacy of different post-first-line agents for advanced GIST following imatinib failure. Network and conventional meta-analysis were carried out using Stata/MP 16.0.

RESULTS:

Ripretinib showed significant improvement in progression-free survival (PFS) rates from the 2nd to the 12th month compared to placebo, while there was virtually no evidence that the rest active agents had a significant benefit at the 12th month. Masitinib, ripretinib, sunitinib, regorafenib, and pimitespib exhibited significantly longer median PFS than placebo, and pairwise comparisons indicated there were no significant differences among masitinib, ripretinib, and sunitinib. These post-first-line agents decreased the risk of disease progression or death by 65% (HR = 0.35, 95% CI: 0.26-0.47) compared to placebo. Ripretinib and sunitinib came into effect earlier and exhibited more consistent overall survival (OS) rate improvements than masitinib and pimitespib, while pairwise comparisons revealed no significant differences in these four active agents concerning the improvement in OS rate. These post-first-line agents decreased the risk of death by 39% (HR = 0.61, 95% CI: 0.44-0.83) over placebo for advanced GIST following imatinib failure.

CONCLUSION:

The active agents in our analysis as post-first-line therapies are able to provide superior clinical efficacy, with improved PFS rate and OS rate at certain time points, as well as absolute values of PFS and OS for advanced GIST. Ripretinib might be the optimal recommendation as a post-first-line treatment for advanced GIST following imatinib failure.

• Authors: Kehan Hu, Hu Zhang, Mingrong Shu, Xingyue Wang
• Journal: Cancer medicine (Cancer Med) Vol. 12 Issue 11 Pg. 12187-12197 (06 2023) ISSN: 2045-7634 [Electronic] United States
• PMID: 37084005 (Publication Type: Meta-Analysis, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Chemical References

• Imatinib Mesylate
• Sunitinib
• masitinib
• ripretinib
• Indoles
• Pyrroles
• Antineoplastic Agents
• Protein Kinase Inhibitors

Topics

• Humans
• Imatinib Mesylate (therapeutic use)
• Gastrointestinal Stromal Tumors (pathology)
• Sunitinib (therapeutic use)
• Network Meta-Analysis
• Gastrointestinal Neoplasms
• Indoles (therapeutic use)
• Pyrroles (therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Protein Kinase Inhibitors (adverse effects)