Association of VEGFR2 polymorphisms with clinical outcomes of anti-angiogenesis therapy in cancer patients: A systematic review and meta-analysis

Background

Some cancer patients derive limited benefit from anti-angiogenic therapy or discontinuation due to adverse reactions. Vascular endothelial growth factor receptor 2 (VEGFR2) plays an important role in regulating angiogenesis in tumors. This study aims to evaluate the association of VEGFR2 polymorphisms with clinical outcomes of anti-angiogenic drugs (AADs) in cancer patients.

Methods

PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to Dec 26, 2023. Studies accessing the association of VEGFR2 polymorphisms with efficacy and/or safety of AADs in patients with solid tumor were included.

Results

A total of 32 studies encompassing 7075 patients were identified. The T allele of rs2305948 (C > T) was significantly associated with worse progression-free survival and overall survival, especially in Asians, patients with the dominant model (CT/TT vs. CC), bevacizumab-treated patients, colorectal cancer patients, and non-small cell lung cancer patients. The C allele of rs2071559 (T > C) was markedly associated with worse PFS and OS, specifically in the dominant model (CC/CT vs. TT), apatinib-treated patients, and non-small cell lung cancer patients. The A allele of rs1870377 (T > A) was significantly associated with improved PFS, particularly in patients with renal cell carcinoma. However, this A allele also significantly increased the risk of hypertension. No significant associations were observed for rs2305948 (G > A), rs11133360 (T > C), and rs12505758 (T > C) with the clinical outcomes of AADs.

Conclusion

Among VEGFR2 polymorphisms, rs2305948 (C > T) and rs2071559 (T > C) were associated with a high risk of disease progression and death, rs1870377 (T > A) was associated with improved PFS but an increased risk of hypertension.