Efficacy and safety comparison of small molecule anti-angiogenic drugs in the treatment of bone and soft tissue sarcomas : a network meta-analysis.

[BACKGROUND] Anti-angiogenic therapy, particularly small-molecule inhibitors targeting the vascular endothelial growth factor receptor (VEGFR), has emerged as a promising approach for treating bone and soft tissue sarcomas. This study aimed to systematically compare the efficacy and safety of different small-molecule anti-angiogenic agents in the treatment of bone and soft tissue sarcomas through a network meta-analysis (NMA).

[METHODS] We conducted a comprehensive search of seven major databases, including China National Knowledge Infrastructure (CNKI), Wanfang, VIP Database (VIP), PubMed, Embase, Cochrane Library, and Web of Science, to collect clinical randomized controlled trials (RCTs) evaluating the use of small-molecule anti-angiogenic drugs in the treatment of bone and soft tissue tumors. R softwarewas used for data analysis. We combined all direct and indirect evidence to compare different treatments in terms of efficacy and safety, reported as hazard ratio (HR) for survival outcomes (progression-free survival and overall survival) and odds ratio (OR) for binary outcomes (objective response rate and disease control rate), with 95% confidence intervals (CIs). The P score was used to rank the side effect risk. This project has been registered on PROSPERO CRD42024584746.

[RESULTS] The initial search yielded 946 records, and 16 studies, involving 1,291 patients, met all criteria. In terms of the disease control rate (DCR), apatinib + chemotherapy is better than chemotherapy alone (OR 0.13 (0.02, 0.92)). In terms of objective response rate (ORR), apatinib + chemo is better than pazopanib + chemotherapy (OR 0.15 (0.02, 0.94)), anlotinib is better than chemo (OR 0.26 (0.07, 0.92)) and pazopanib + chemo (OR 0.15 (0.03, 0.85)). The side effects of different treatments vary.

[CONCLUSIONS] Short-term efficacy of small-molecule anti-angiogenic TKIs varied across bone and soft tissue sarcomas, with trends favoring apatinib plus chemotherapy and anlotinib. However, substantial heterogeneity across studies, including sarcoma subtypes and prior therapies, limits definitive conclusions regarding comparative efficacy. A multidisciplinary team is needed to better manage the side effects.