Pharmacogenetic and clinical risk factors for bevacizumab-related gastrointestinal hemorrhage in prostate cancer patients treated on CALGB 90401 (Alliance) Journal Article
| Authors: | 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. |
| Article Title: | Pharmacogenetic and clinical risk factors for bevacizumab-related gastrointestinal hemorrhage in prostate cancer patients treated on CALGB 90401 (Alliance) |
| 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 × 10−8) 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. © The Author(s) 2024. |
| Keywords: | adult; controlled study; aged; major clinical study; single nucleotide polymorphism; genetics; prednisone; bevacizumab; placebo; gastrointestinal hemorrhage; cancer patient; prospective study; disease association; multiple cycle treatment; prevalence; cohort analysis; genetic association; genotype; gene frequency; genome-wide association study; risk factors; risk factor; docetaxel; prostate cancer; prostatic neoplasms; disease severity; prostate tumor; pharmacogenetics; antithrombocytic agent; anticoagulant agent; randomized controlled trial (topic); european; cancer prognosis; disease burden; very elderly; humans; human; male; article; metastatic castration resistant prostate cancer; disease risk assessment |
| Journal Title: | Pharmacogenomics Journal |
| Volume: | 24 |
| Issue: | 2 |
| ISSN: | 1470-269X |
| Publisher: | Springernature |
| Date Published: | 2024-01-01 |
| Start Page: | 6 |
| Language: | English |
| DOI: | 10.1038/s41397-024-00328-z |
| PUBMED: | 38438359 |
| PROVIDER: | scopus |
| PMCID: | PMC10912014 |
| DOI/URL: | |
| Notes: | Source: Scopus |
