Systematic Literature Review and Meta-Analysis of HER2 Amplification, Overexpression, and Positivity in Colorectal Cancer

A partir d'une revue systématique de la littérature (52 études, 17 589 patients), cette méta-analyse estime la proportion de patients présentant une tumeur colorectale avec expression, surexpression ou amplification du récepteur HER2

Résumé en anglais

Background : Colorectal cancer (CRC) is the second most common cause of cancer death globally. Recent clinical trials suggest an emerging role for human epidermal growth factor receptor 2 (HER2) as a potential clinically relevant biomarker in CRC. Testing for HER2 in CRC is not standard practice; consequently, the prevalence of HER2 positivity (HER2+) in patients with CRC remains uncertain.

Methods : A systematic literature review and meta-analysis were conducted to generate estimates of proportions of patients with CRC with HER2 overexpression/HER2 amplification, and HER2 + (either overexpression or amplification), overall and in patients with rat sarcoma virus (RAS) wild type (WT) cancer. HER2+ was defined as (1) immunohistochemistry (IHC) 3+, (2) IHC 2+ and in situ hybridization (ISH+); or (3) next-generation sequencing positive.

Results : Of 224 studies identified with information on HER2 in CRC, 52 studies used an FDA-approved assay and were selected for further analysis. Estimated HER2+ rate was 4.1% (95% confidence interval [CI] = 3.4% to 5.0%) overall (n = 17,589). HER2+ rates were significantly higher in RAS WT (6.1% [95% CI = 5.4% to 6.9%]) vs RAS mutant CRC (1.1% [95% CI = 0.3% to 4.4%; P<.0001]). Despite limited clinical information, we confirmed enrichment of HER2+ CRC in patients with microsatellite stable and left-sided CRC.

Conclusion : This meta-analysis provides an estimate of HER2+ CRC and confirms enrichment of HER2 in microsatellite stable, left-sided, RAS-WT CRC tumors. Our work is important given the recently described clinical efficacy of HER2-targeted therapies in HER2+ CRC and informs strategies for incorporation of HER2 testing into standard of care.