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

Authors

• Jai N Patel
• Chen Jiang
• Kouros Owzar
• Daniel L Hertz
• Janey Wang
• Flora A Mulkey
• William K Kelly
• Susan Halabi
• Yoichi Furukawa
• Cameron Lassiter
• Susan G Dorsey
• Paula N Friedman
• Eric J Small
• Michael A Carducci
• Michael J Kelley
• Yusuke Nakamura
• Michiaki Kubo
• Mark J Ratain
• Michael J Morris
• Howard L McLeod

Publication/Presentation Date

3-4-2024

Abstract

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

Volume

24

Issue

2

First Page

6

Last Page

6

ISSN

1473-1150

Published In/Presented At

Patel, J. N., Jiang, C., Owzar, K., Hertz, D. L., Wang, J., Mulkey, F. A., Kelly, W. K., Halabi, S., Furukawa, Y., Lassiter, C., Dorsey, S. G., Friedman, P. N., Small, E. J., Carducci, M. A., Kelley, M. J., Nakamura, Y., Kubo, M., Ratain, M. J., Morris, M. J., & McLeod, H. L. (2024). Pharmacogenetic and clinical risk factors for bevacizumab-related gastrointestinal hemorrhage in prostate cancer patients treated on CALGB 90401 (Alliance). The pharmacogenomics journal, 24(2), 6. https://doi.org/10.1038/s41397-024-00328-z

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

38438359

Department(s)

Administration and Leadership

Document Type

Article