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Pharmacogenetic and clinical risk factors for bevacizumab-related gastrointestinal hemorrhage in prostate cancer patients treated on CALGB 90401 (Alliance).

Publication ,  Journal Article
Patel, JN; Jiang, C; Owzar, K; Hertz, DL; Wang, J; Mulkey, FA; Kelly, WK; Halabi, S; Furukawa, Y; Lassiter, C; Dorsey, SG; Friedman, PN ...
Published in: Pharmacogenomics J
March 4, 2024

The objective of this study was to discover clinical and pharmacogenetic factors associated with bevacizumab-related gastrointestinal hemorrhage in Cancer and Leukemia Group B (Alliance) 90401. Patients with metastatic castration-resistant prostate cancer received docetaxel and prednisone ± bevacizumab. Patients were genotyped using Illumina HumanHap610-Quad and assessed using cause-specific risk for association between single nucleotide polymorphisms (SNPs) and gastrointestinal hemorrhage. In 1008 patients, grade 2 or higher gastrointestinal hemorrhage occurred in 9.5% and 3.8% of bevacizumab (n = 503) and placebo (n = 505) treated patients, respectively. Bevacizumab (P < 0.001) and age (P = 0.002) were associated with gastrointestinal hemorrhage. In 616 genetically estimated Europeans (n = 314 bevacizumab and n = 302 placebo treated patients), grade 2 or higher gastrointestinal hemorrhage occurred in 9.6% and 2.0% of patients, respectively. One SNP (rs1478947; HR 6.26; 95% CI 3.19-12.28; P = 9.40 × 10-8) surpassed Bonferroni-corrected significance. Grade 2 or higher gastrointestinal hemorrhage rate was 33.3% and 6.2% in bevacizumab-treated patients with the AA/AG and GG genotypes, versus 2.9% and 1.9% in the placebo arm, respectively. Prospective validation of these findings and functional analyses are needed to better understand the genetic contribution to treatment-related gastrointestinal hemorrhage.

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Published In

Pharmacogenomics J

DOI

EISSN

1473-1150

Publication Date

March 4, 2024

Volume

24

Issue

2

Start / End Page

6

Location

United States

Related Subject Headings

  • Risk Factors
  • Prostatic Neoplasms
  • Pharmacology & Pharmacy
  • Pharmacogenetics
  • Male
  • Humans
  • Gastrointestinal Hemorrhage
  • Bevacizumab
  • 3214 Pharmacology and pharmaceutical sciences
  • 1115 Pharmacology and Pharmaceutical Sciences
 

Citation

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Patel, J. N., Jiang, C., Owzar, K., Hertz, D. L., Wang, J., Mulkey, F. A., … McLeod, H. L. (2024). Pharmacogenetic and clinical risk factors for bevacizumab-related gastrointestinal hemorrhage in prostate cancer patients treated on CALGB 90401 (Alliance). Pharmacogenomics J, 24(2), 6. https://doi.org/10.1038/s41397-024-00328-z
Patel, Jai N., Chen Jiang, Kouros Owzar, Daniel L. Hertz, Janey Wang, Flora A. Mulkey, William K. Kelly, et al. “Pharmacogenetic and clinical risk factors for bevacizumab-related gastrointestinal hemorrhage in prostate cancer patients treated on CALGB 90401 (Alliance).Pharmacogenomics J 24, no. 2 (March 4, 2024): 6. https://doi.org/10.1038/s41397-024-00328-z.
Patel JN, Jiang C, Owzar K, Hertz DL, Wang J, Mulkey FA, et al. Pharmacogenetic and clinical risk factors for bevacizumab-related gastrointestinal hemorrhage in prostate cancer patients treated on CALGB 90401 (Alliance). Pharmacogenomics J. 2024 Mar 4;24(2):6.
Patel, Jai N., et al. “Pharmacogenetic and clinical risk factors for bevacizumab-related gastrointestinal hemorrhage in prostate cancer patients treated on CALGB 90401 (Alliance).Pharmacogenomics J, vol. 24, no. 2, Mar. 2024, p. 6. Pubmed, doi:10.1038/s41397-024-00328-z.
Patel JN, Jiang C, Owzar K, Hertz DL, Wang J, Mulkey FA, Kelly WK, Halabi S, Furukawa Y, Lassiter C, Dorsey SG, Friedman PN, Small EJ, Carducci MA, Kelley MJ, Nakamura Y, Kubo M, Ratain MJ, Morris MJ, McLeod HL. Pharmacogenetic and clinical risk factors for bevacizumab-related gastrointestinal hemorrhage in prostate cancer patients treated on CALGB 90401 (Alliance). Pharmacogenomics J. 2024 Mar 4;24(2):6.

Published In

Pharmacogenomics J

DOI

EISSN

1473-1150

Publication Date

March 4, 2024

Volume

24

Issue

2

Start / End Page

6

Location

United States

Related Subject Headings

  • Risk Factors
  • Prostatic Neoplasms
  • Pharmacology & Pharmacy
  • Pharmacogenetics
  • Male
  • Humans
  • Gastrointestinal Hemorrhage
  • Bevacizumab
  • 3214 Pharmacology and pharmaceutical sciences
  • 1115 Pharmacology and Pharmaceutical Sciences