Predictive value of chromosome 18q11.2-q12.1 loss for benefit from bevacizumab in metastatic colorectal cancer: A post hoc analysis of the randomized phase III-trial AGITG-MAX
- Author(s)
- Van Dijk, E; van Werkhoven, E; Asher, R; Mooi, JK; Espinoza, D; van Essen, HF; van Tinteren, H; van Grieken, NCT; Punt, CJA; Tebbutt, NC; Ylstra, B;
- Details
- Publication Year 2022-10-01,Volume 151,Issue #7,Page 1166-1174
- Journal Title
- International Journal of Cancer
- Publication Type
- Research article
- Abstract
- The VEGF-A monoclonal antibody bevacizumab is currently recommended for first-line treatment of all metastatic colorectal cancer (mCRC) patients. Cost-benefit ratio and side-effects however necessitate patient selection. A large retrospective yet nonrandomized study showed that patients with loss of chromosome 18q11.2-q12.1 in the tumor and treated with bevacizumab have 3 months improved median progression-free (PFS) and overall survival (OS) benefit compared to patients without this loss and/or treatment modality. Implementation for loss of chromosome 18q11.2-q12.1 as a marker in clinical practice mandates evidence in a randomized controlled trial for bevacizumab. Of the trials with randomization of chemotherapy vs chemotherapy with bevacizumab, the AGITG-MAX trial was the only one with tumor materials available. Chromosome 18q11.2-q12.1 copy number status was measured for 256 AGITG-MAX trial patients and correlated with PFS according to a predefined analysis plan with marker-treatment interaction as the primary end-point. Chromosome 18q11.2-q12.1 losses were detected in 71% of patients (181/256) characteristic for mCRC. Consistent with the nonrandomized study, significant PFS benefit of bevacizumab was observed in patients with chromosome 18q11.2-q12.1 loss (P = .009), and not in patients without 18q loss (P = .67). Although significance for marker-treatment interaction was not reached (P(interaction) = .28), hazard ratio and 95% confidence interval of this randomized cohort (HR(interaction) = 0.72; 95% CI = 0.39-1.32) shows striking overlap with the nonrandomized study cohorts (HR(interaction) = 0.41; 95% CI = 0.32-0.8) supported by a nonsignificant Cochrane chi(2) test (P = .11) for heterogeneity. We conclude that post hoc analysis of the AGITG-MAX RCT provides supportive evidence for chromosome 18q11.2-q12.1 as a predictive marker for bevacizumab in mCRC patients.
- Keywords
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use; Bevacizumab/therapeutic use; Chromosome Deletion; Chromosomes; *Colonic Neoplasms/genetics; *Colorectal Neoplasms/drug therapy/genetics/pathology; Disease-Free Survival; Fluorouracil/therapeutic use; Humans; *Rectal Neoplasms/drug therapy; Retrospective Studies; anti-VEGF monoclonal antibody; bevacizumab; chromosome 18q; metastatic colorectal cancer; predictive biomarker; randomized controlled trial
- Department(s)
- Medical Oncology
- PubMed ID
- 35489024
- Publisher's Version
- https://doi.org/10.1002/ijc.34061
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-04-24 07:51:36
Last Modified: 2025-04-24 07:52:36