Immune checkpoint inhibitors combined with tyrosine kinase inhibitors for soft-tissue sarcomas: a systematic review and single-arm meta-analysis

INTRODUCTION: Soft tissue sarcomas (STS) are a rare and diverse group of mesodermal-origin cancers with limited systemic treatment options in advanced-stage disease. Recent evidence suggests that combination therapies involving tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor receptor (VEGFR) and immune checkpoint inhibitors (ICIs) may enhance clinical outcomes. METHODS: We conducted a systematic review and meta-analysis. Databases were searched for prospective clinical trials evaluating ICIs and VEGFR-TKIs combination therapy in adults with advanced STS. Primary outcomes were objective response rating (ORR), overall survival (OS), and progression-free survival (PFS). A subgroup analysis was performed for alveolar soft part sarcoma (ASPS). We extracted the grade ≥3 adverse events (AE) as the safety outcomes of interest. Random-effects modeling was used for analysis, and continuous endpoints were pooled using the mean difference (MD) with a random effects model. RESULTS: Eight non-randomized phase II trials involving 332 patients were eligible. The pooled ORR was 33% (95% CI: 17%-49%) and median PFS was 7.1 months (95% CI: 5.5-8.6). In the ASPS subgroup, the ORR reached 73% (95% CI: 64%-82%). Grade ≥3 AEs occurred in 40% of patients, most commonly hypothyroidism, diarrhea, and elevated hepatic enzymes. CONCLUSION: The combination of ICIs and TKIs demonstrated promising efficacy, particularly in ASPS, with outcomes favorable to the historical benchmarks. Future studies should incorporate biomarker-driven and histology-specific approaches to optimize patient selection and improve the outcomes.