A systematic review and network meta-analysis of the efficacy and safety of third-line and over third-line therapy after imatinib and TKI resistance in advanced gastrointestinal stromal tumor

Abstract

Tyrosine kinase inhibitors (TKIs) have greatly improved the prognosis of unresectable and metastatic gastrointestinal stromal tumors (GISTs) in the last two decades. Imatinib and sunitinib are recommended as first-line and second-line therapies, respectively. However, there is a lack of precision therapy for refractory GISTs regarding therapy after imatinib and sunitinib. We comprehensively searched electronic databases, including PubMed, EMBASE, Web of Science, Cochrane Library, and ClinicalTrials, from inception to October 2022. Randomized controlled trials featuring comparisons with third-line or over third-line therapies against GISTs were eligible. The primary outcome was progression-free survival (PFS). All network calculations were performed using random effect models, and the ranking of regimens were numerically based on the surface under the cumulative ranking (SUCRA) statistics. A total of seven studies were eligible for inclusion in this network meta-analysis. After analysis, ripretinib was ranked at the top in progression-free survival (PFS), overall survival (OS), and disease control rate (DCR) (SUCRA statistics: 83.1%, 82.5%, and 86.5%, respectively), whereas nilotinib and pimitespib presented better tolerability (SUCRA statistics: 64.9% and 63.8%, respectively). We found that regorafenib seemed more reliable for clinical administration, and ripretinib showed good effectiveness for the over third-line therapy. Precise targeted therapy is a critical direction for the future treatment of GIST, and more high-quality studies of new agents are expected.