Genetic variant predicts bevacizumab-induced hypertension in ECOG-5103 and ECOG-2100 BRITISH JOURNAL OF CANCER Schneider, B. P., Li, L., Shen, F., Miller, K. D., Radovich, M., O'Neill, A., Gray, R. J., Lane, D., Flockhart, D. A., Jiang, G., Wang, Z., Lai, D., Koller, D., Pratt, J. H., Dang, C. T., Northfelt, D., Perez, E. A., Shenkier, T., Cobleigh, M., Smith, M. L., Railey, E., Partridge, A., Gralow, J., Sparano, J., Davidson, N. E., Foroud, T., Sledge, G. W. 2014; 111 (6): 1241-1248


Bevacizumab has broad anti-tumour activity, but substantial risk of hypertension. No reliable markers are available for predicting bevacizumab-induced hypertension.A genome-wide association study (GWAS) was performed in the phase III bevacizumab-based adjuvant breast cancer trial, ECOG-5103, to evaluate for an association between genotypes and hypertension. GWAS was conducted in those who had experienced systolic blood pressure (SBP) >160?mm?Hg during therapy using binary analysis and a cumulative dose model for the total exposure of bevacizumab. Common toxicity criteria (CTC) grade 3-5 hypertension was also assessed. Candidate SNP validation was performed in the randomised phase III trial, ECOG-2100.When using the phenotype of SBP>160?mm?Hg, the most significant association in SV2C (rs6453204) approached and met genome-wide significance in the binary model (P=6.0 × 10(-8); OR=3.3) and in the cumulative dose model (P=4.7 × 10(-8); HR=2.2), respectively. Similar associations with rs6453204 were seen for CTC grade 3-5 hypertension but did not meet genome-wide significance. Validation study from ECOG-2100 demonstrated a statistically significant association between this SNP and grade 3/4 hypertension using the binary model (P-value=0.037; OR=2.4).A genetic variant in SV2C predicted clinically relevant bevacizumab-induced hypertension in two independent, randomised phase III trials.

View details for DOI 10.1038/bjc.2014.430

View details for Web of Science ID 000341910900025

View details for PubMedCentralID PMC4453857