We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Impact of Anti-EGFR Therapies on HER2-Positive Metastatic Colorectal Cancer: A Systematic Literature Review and Meta-Analysis of Clinical Outcomes.
- Authors
Bekaii-Saab, Tanios S; Lach, Krzysztof; Hsu, Ling-I; Siadak, Muriel; Stecher, Mike; Ward, James; Beckerman, Rachel; Strickler, John H
- Abstract
Background HER2 overexpression/amplification in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC) may be associated with resistance to standard-of-care anti-EGFR therapies. Given the lack of comprehensive investigations into this association, we assessed the prognostic or predictive effect of HER2 amplification/overexpression on anti-EGFR treatment outcomes. Methods A systematic review of MEDLINE, Embase, and Cochrane Library (2001-2021) identified studies evaluating progression-free survival (PFS), overall response rate (ORR), and overall survival (OS) in HER2-positive vs. HER2-negative patients with RAS WT mCRC who received anti-EGFR treatments and whose HER2 status was known. Meta-analyses of proportions (ORR) and hazard ratios (PFS, OS) were performed using random-effect models with pre-specified sensitivity analyses. Results Five high-quality retrospective cohort studies were included in the meta-analyses representing 594 patients with mCRC. All patients received anti-EGFR treatment, either as monotherapy or in combination with chemotherapy. Meta-analysis of PFS demonstrated a 2.84-fold higher risk of death or progression (95% CI, 1.44-5.60) in patients with HER2-positive (vs. HER2-negative) RAS WT mCRC treated with anti-EGFR regimens. The odds of response to anti-EGFR treatment were 2-fold higher in HER2-negative vs. HER2-positive (odds ratio, 1.96 [95% CI, 1.10-3.48]). Differences in OS were not statistically significant. Sensitivity analyses confirmed the robustness of the base-case estimates. Conclusions While this study could not account for all confounding factors, in patients with RAS WT mCRC who received anti-EGFR therapy, HER2 overexpression/amplification was associated with worse PFS and ORR and may therefore predict poorer outcomes. HER2 testing is important to inform treatment decisions and could optimize outcomes for patients.
- Subjects
MEDICAL databases; META-analysis; MEDICAL information storage &; retrieval systems; CONFIDENCE intervals; EPIDERMAL growth factor receptors; METASTASIS; RETROSPECTIVE studies; COLORECTAL cancer; TREATMENT effectiveness; GENE expression; DECISION making; DESCRIPTIVE statistics; RESEARCH funding; MEDLINE; PROGRESSION-free survival; SENSITIVITY &; specificity (Statistics); OVERALL survival
- Publication
Oncologist, 2023, Vol 28, Issue 10, p885
- ISSN
1083-7159
- Publication type
Article
- DOI
10.1093/oncolo/oyad200