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Effect of HER2 Overexpression or Amplification on Resistance to Anti-EGFR Treatment Among Patients with RAS Wild-Type Metastatic Colorectal Cancer

Allison Casey 

There was an association found between HER2 overexpression/amplification and worse progression-free survival (PFS) and overall response rate (ORR) among patients with RAS wild-type metastatic colorectal cancer who received anti-EGFR therapy.

Dr Tanos Bekaii-Saab, MD, Mayo Clinic, Phoenix, Arizona, and coauthors wrote, “HER2 overexpression/amplification in patients with RAS wild-type metastatic colorectal cancer may be associated with resistance to standard-of-care anti-EGFR therapies.” With conflicting evidence and no current ongoing clinical trials in this issue, there is a need for “a comprehensive review and synthesis of existing literature.”

This systemic review identified studies which evaluated PFS, ORR, and overall survival among patients who have RAS wild-type metastatic colorectal cancer and were treated with anti-EGFR therapies who were HER2-positive vs HER2-negative. Of the 2 studies included, there were 594 patients represented, all who received anti-EGFR therapy as either monotherapy or in combination with chemotherapy.

In the meta-analysis, PFS demonstrated a 2.84-fold higher risk of death or progression when patients were HER2-positive compared to HER2-negative. The odds of response to the anti-EGFR therapy were 2-fold higher among patients who were HER2-negative vs HER2-positive. The differences between overall survival was not significant.

According to Dr Bekaii-Saab et al, because of the association between HER2 overexpression/amplification and worse PFS and ORR, HER2 overexpression/amplification in this population “may therefore predict poorer outcomes.” They added, “HER2 testing is important to inform treatment decisions and could optimize outcomes for patients.”


Source:

Bekaii-Saab TS, Lach K, Hsu Ling-I, et al. Impact of anti-EGFR therapies on HER2-positive metastatic colorectal cancer: a systematic literature review and meta-analysis of clinical outcomes. Oncologist. Published July 18, 2023. doi:10.1093/oncolo/oyad200