The optimal choice and combination strategy of vascular-targeting therapy for patients with advanced soft tissue sarcoma: A systematic review and network meta-analysis.

Abstract

e23532 Background: Soft tissue sarcomas (STS) are rare, heterogeneous tumors with poor prognosis, often characterized by high recurrence rates and limited response to conventional chemotherapy, especially in advanced stages. Vascular-targeting agents (VTAs) have shown promising efficacy in treating advanced STS, yet optimal agent selection and combination strategies remain undetermined. Methods: This systematic review and network meta-analysis evaluated the efficacy and safety of various VTAs used as monotherapy or in combination with chemotherapy or immunotherapy for advanced STS. We searched PubMed, Embase and Cochrane Library for randomized controlled trials (RCTs) involving VTAs in advanced STS. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and treatment-related adverse events (TRAEs) were assessed. Pooled hazard ratios (HRs) and odds ratios (ORs) with credible intervals (CrIs) were generated. A Bayesian random-effects model was used to rank different treatments based on surface under the cumulative ranking curve (SUCRA) values. Results: A total of 24 articles covering 22 studies were included in this meta-analysis. All VTA-containing interventions demonstrated improved efficacy over placebo in either PFS or OS. Among these, chemotherapy combined with large molecular monoclonal antibodies showed a trend toward prolonged OS compared with tyrosine kinase inhibitors (TKI) (HR 0.49; 95% CI 0.25-0.99). SUCRA values indicated that anti-angiogenic monoclonal antibodies plus chemotherapy ranked in the top three for PFS (66.33%), OS (82.70%), and ORR (65.11%). Additionally, TKI combined with chemotherapy and vascular-disrupting agents plus chemotherapy were identified as the most likely to enhance PFS, OS, and ORR. TKI-containing regimens were associated with higher incidences of hypertension and diarrhea, while chemotherapy-containing strategies showed higher incidences of anemia, fatigue and constipation. Conclusions: Anti-angiogenic monoclonal antibody plus chemotherapy showed relatively better efficacy than other drugs and combination strategies in short-term efficacy and long-term survival in patients with advanced STS. All the TRAEs were moderate and well-tolerated.