The efficacy of immunotherapy in the treatment of tyrosine kinase inhibitor-refractory gastrointestinal stromal tumors: a systematic review and meta-analysis

Abstract

Background

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. The advent of tyrosine kinase inhibitors (TKIs), such as imatinib, has significantly improved clinical outcomes in patients with GISTs by delaying metastasis and prolonging survival. However, most patients eventually develop resistance to TKIs, limiting long-term disease control. Immunotherapy has demonstrated durable responses in various solid tumors and has emerged as a potential treatment strategy for TKI-refractory GISTs. This study aimed to systematically evaluate the efficacy and safety of immunotherapy in patients with advanced or recurrent GIST, particularly those who have failed previous TKI therapy, to inform future clinical decision-making and research directions.

Methods

A systematic literature search of PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov was conducted for studies published before June 23, 2025. The inclusion criteria focused on immunotherapy interventions in patients with histologically confirmed GIST. Study selection, data extraction, and risk of bias assessments were performed independently by 2 reviewers according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Joanna Briggs Institute checklist was used for quality appraisal. Random-effects models were used to pool estimates of clinical benefit rate (CBR), objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Generalized linear mixed models (GLMM) were used to account for cohorts with extreme values. This review protocol was registered with the International Registry of Systematic Reviews (registration number: CRD42024496866).

Results

A total of 9 studies involving 169 patients were included. The pooled CBR was 41.69% (95% CI, 26.99%–58.03%), and the ORR was 16.49% (95% CI, 6.25%–36.91%), both with moderate to high heterogeneity. GLMM adjustments, which incorporated additional extreme value cohorts, yielded a corrected CBR of 46.39% (95% CI, 28.85%–64.88%) and ORR of 13.23% (95% CI, 4.21%–34.56%). The pooled median PFS across 7 cohorts was 6.11 months (95% CI, 2.63–9.59), and the OS, which was calculated using 2 models, ranged from 15.53 to 17.01 months, depending on the data imputation strategy.

Conclusion

This meta-analysis suggests that immunotherapy provides modest yet clinically meaningful efficacy in patients with advanced or treatment-refractory GIST. Despite considerable heterogeneity among studies, the observed trends in response and survival outcomes support immunotherapy as a viable treatment option. Further large-scale, biomarker-driven clinical trials are warranted to validate these findings and guide personalized therapeutic strategies.