Tyrosine kinase inhibitors demonstrated an objective response rate of 23% (95% CI, 11.2-37.1%) in patients with advanced Ewing sarcoma who received at least one prior line of therapy.
Meta-Analysis (n=257)
Do tyrosine kinase inhibitors improve objective response rate in patients with advanced Ewing sarcoma who received at least one prior line of therapy?
Anti-angiogenic tyrosine kinase inhibitors demonstrate meaningful anti-tumoral activity in patients with advanced, previously treated Ewing sarcoma, with a pooled objective response rate of 23%.
Background/Objectives: Standard treatment of multiply relapsed Ewing sarcoma remains to be established. Recent studies evaluating tyrosine kinase inhibitors (TKIs) with anti-angiogenic properties have shown encouraging results. Therefore, we conducted a systematic review and meta-analysis to explore the efficacy and safety of TKIs in patients with Ewing sarcoma. Methods: We comprehensively searched PubMed, Embase, and Cochrane databases for clinical trials (CTs) and cohort studies assessing TKIs in the treatment of advanced Ewing sarcoma patients who received at least one prior line of therapy. The main outcome was objective response rate (ORR). All analyses were conducted using R software (v.4.2.2), employing random effects models with 95% confidence intervals (CIs). Results: We included 14 studies (seven phase II CT and seven retrospective cohorts), comprising 257 patients. The following TKIs were evaluated: cabozantinib, regorafenib, apatinib, anlotinib, sorafenib, lenvatinib, sunitinib, fruquintinib, and imatinib. In a pooled analysis of all Ewing sarcoma patients treated with TKIs, the ORR was 23% (95% CI, 11.2–37.1%) and the DCR was 61.1% (95% CI, 47.3–74.2%). Responses were numerically higher but statistically nonsignificant between clinical trials and real-world studies. The analysis including only single-agent TKIs showed better responses for anlotinib and apatinib, yet these drugs are not available in Western countries. Among the FDA-approved TKIs, superior outcomes were noted with single-agent cabozantinib. (ORR: 21.6%) and regorafenib (ORR: 11.3%). Several studies did not report toxicity data exclusively for Ewing sarcoma patients; thus, conclusions about toxicity are mostly based on the general population of studies and may not be fully representative of Ewing sarcoma patients. Conclusions: Anti-angiogenic TKIs have shown important anti-tumoral activity in patients with Ewing sarcoma. Efficacy was consistently seen in both clinical trials and real-world studies. Nonetheless, there are important differences in study design and population that may limit our interpretation of efficacy and toxicity findings.
Michelon et al. (Fri,) conducted a meta-analysis in Advanced Ewing Sarcoma (n=257). Tyrosine kinase inhibitors (TKIs) was evaluated on Objective response rate (ORR) (95% CI 11.2-37.1). Tyrosine kinase inhibitors demonstrated an objective response rate of 23% (95% CI, 11.2-37.1%) in patients with advanced Ewing sarcoma who received at least one prior line of therapy.