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

• Published in: The pharmacogenomics journal 2024-04, Vol.24 (2), p.6, Article 6
• Main Authors: Patel, Jai N., Jiang, Chen, Owzar, Kouros, Hertz, Daniel L., Wang, Janey, Mulkey, Flora A., Kelly, William K., Halabi, Susan, Furukawa, Yoichi, Lassiter, Cameron, Dorsey, Susan G., Friedman, Paula N., Small, Eric J., Carducci, Michael A., Kelley, Michael J., Nakamura, Yusuke, Kubo, Michiaki, Ratain, Mark J., Morris, Michael J., McLeod, Howard L.
• Format: Article
• Language: English
• Subjects: 45; 45/43; 631/208/205; 692/499; Bevacizumab; Bevacizumab - adverse effects; Biomedical and Life Sciences; Biomedicine; Castration; Gastrointestinal Hemorrhage - chemically induced; Gastrointestinal Hemorrhage - genetics; Gene Expression; Hemorrhage; Human Genetics; Humans; Male; Metastases; Oncology; Patients; Pharmacogenetics; Pharmacotherapy; Placebos; Prednisone; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - genetics; Psychopharmacology; Risk Factors; Single-nucleotide polymorphism
• ISSN: 1470-269X; 1473-1150; 1473-1150
• DOI: 10.1038/s41397-024-00328-z

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