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Efficacy and safety of vascular-targeting agents in advanced soft tissue sarcoma: a systematic review and network
Yan Wang1, Hangcheng Xu1, Qiang Sa1
1Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Background:
Soft tissue sarcomas (STS) are rare, heterogeneous tumors with poor prognosis, often characterized by high recurrence rates and limited response to conventional chemotherapy in advanced stages. Vascular-targeting agents (VTA) have shown promising efficacy for STS in numerous clinical trials; however, the optimal agent and combination strategies remain undetermined.
Objectives:
This work aims to compare the clinical efficacy and adverse events of different VTA-containing regimens for patients with STS.
Design:
This study is a systematic review and network meta-analysis.
Data Sources And Methods:
We searched PubMed, Embase, and the Cochrane Library for eligible randomized clinical trials. All trials with VTA as monotherapy or VTA-included regimens in the experimental or control groups were selected, except for some specific histological subtypes. Pooled hazard ratios (HRs) for survival data and odds ratios for objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events with credible intervals were generated using R software. A Bayesian random-effects model was applied to rank different treatments based on the surface under the cumulative ranking curve (SUCRA) values.
Results:
Seventeen articles covering 15 studies were included. Pairwise comparisons demonstrated prolonged progression-free survival (PFS) for tyrosine kinase inhibitor (TKI) versus placebo (HR 0.50, 95% confidence interval (CI) 0.32-0.83) and prolonged overall survival (OS) for monoclonal antibody plus chemotherapy versus placebo (HR 0.42, 95% CI 0.19-0.89). Vascular-disrupting agents (VDA) plus chemotherapy were ranked highest for OS (87.05%) and ORR (89.66%). TKI plus chemotherapy and TKI plus immunotherapy had higher SUCRA values for PFS (68.21%) and DCR (82.29%). TKI-based regimens were associated with higher incidences of hypertension, diarrhea, and elevated transaminase levels, whereas chemotherapy-based strategies resulted in higher incidences of hematological toxicity and constipation.
Conclusion:
VTA-containing regimens showed promising activity and tolerability in patients with advanced STS. Combination regimens with TKI showed better efficacy for PFS and DCR. Novel VDA combined with chemotherapy showed potential to prolong OS and improve ORR.
Trial Registration:
PROSPERO website (registration number: CRD42024588134).
Insights
Vascular-targeting agents (VTA) show promise for soft tissue sarcomas (STS). Combination therapies, particularly with tyrosine kinase inhibitors (TKI) or vascular-disrupting agents (VDA), offer improved survival and response rates in advanced STS.
Area of Science:
- Oncology
- Medical Pharmacology
- Clinical Trials
Background:
- Soft tissue sarcomas (STS) are rare, aggressive tumors with poor prognoses and high recurrence rates.
- Advanced STS often shows limited response to traditional chemotherapy.
- Vascular-targeting agents (VTA) present a promising therapeutic avenue, but optimal strategies require further investigation.
Purpose of the Study:
- To systematically compare the clinical efficacy and safety of various VTA-containing regimens for STS patients.
- To identify the most effective VTA-based treatment strategies for advanced STS.
Main Methods:
- A systematic review and Bayesian network meta-analysis of randomized clinical trials.
- Searched major databases (PubMed, Embase, Cochrane Library) for eligible trials involving VTA monotherapy or combination regimens.
- Analyzed progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events.
Main Results:
- Vascular-disrupting agents (VDA) plus chemotherapy demonstrated the highest rankings for OS and ORR.
- Tyrosine kinase inhibitor (TKI) combinations showed superior PFS and DCR.
- TKI-based regimens were linked to hypertension and gastrointestinal side effects, while chemotherapy led to hematological toxicity.
Conclusions:
- VTA-containing regimens are active and generally well-tolerated in advanced STS.
- Combination strategies, especially those involving TKIs, enhance PFS and DCR.
- VDA plus chemotherapy holds potential for improving OS and ORR in advanced STS.
