Treatment research after failure of fourth‐line standard therapy for advanced gastrointestinal stromal tumors: A review

Abstract Tyrosine kinase inhibitors (TKIs) are the primary therapeutic agents for patients with gastrointestinal stromal tumors (GISTs). Imatinib has demonstrated efficacy as a first‐line treatment for intermediate‐ and high‐risk localized GISTs, as well as for relapsed or metastatic progressive GISTs. However, some patients develop resistance to imatinib, which leads to accelerated progression, complex genetic mutations, and high spatiotemporal heterogeneity. The efficacy of the second‐, third‐, and fourth‐line standard treatments recommended by the latest National Comprehensive Cancer Network guidelines is limited, and no unified treatment protocol after the failure of fourth‐line therapy exists. Therefore, exploring new treatment modalities is crucial. This article reviews recent research on treatment strategies after the failure of standard treatments for progressive GISTs, including the alternating or combined use of different TKIs, radiotherapy, and immunotherapy. It also discusses relevant advances presented at international conferences, which provide new evidence‐based support for clinical decision‐making.