Abstract 376P
Background
HER2 overexpression/amplification in patients with RAS wild-type (WT) mCRC may be associated with resistance to standard of care anti-EGFR therapies. However, there are no meta-analyses investigating this association. Our objective was to assess the predictive effect of HER2 amplification/overexpression on anti-EGFR treatment outcomes.
Methods
A systematic review of MEDLINE, Embase, and Cochrane Library, covering 2001-2021, was conducted (from Jun-Aug 2021). Studies evaluating overall response rate (ORR), progression-free survival (PFS) or overall survival (OS) in HER2-positive vs HER2-negative, RAS WT mCRC patients who received anti-EGFR treatments and whose HER2 status was determined by immunohistochemistry, in-situ hybridization or tissue-based next-generation sequencing were included in the review. Study quality was assessed using Newcastle-Ottawa scale. 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, with 620 CRC patients. The majority of patients had left-sided mCRC tumors (73% to 90%). All patients received anti-EGFR treatment, either as monotherapy or in combination with standard chemotherapy. Based on meta-analysis of ORR, the odds of response to anti-EGFR treatment were 49% lower in HER2-positive vs HER2-negative mCRC patients (odds ratio, 0.51 [95% CI, 0.29 to 0.91]). Meta-analysis of PFS demonstrated a 2.84 higher risk of death or progression (95% CI, 1.44 to 5.60) in HER2-positive vs. HER2-negative RAS WT mCRC patients treated with anti-EGFR regimens. Three studies reported OS and the meta-analysis for OS was not statistically significant. Sensitivity analyses confirmed the robustness of the base case estimates.
Conclusions
In RAS WT mCRC patients who received anti-EGFR therapy, HER2 overexpression/amplification was associated with worse PFS and ORR, and may therefore predict worse outcomes with therapy. HER2 testing should be considered to help optimize treatment choices.
Clinical trial identification
Editorial acknowledgement
Medical writing support was provided by Joshua Fink, PhD, of Curo Consulting, a division of Envision Pharma Group, and funded by Seagen Inc.
Legal entity responsible for the study
Seagen Inc.
Funding
Seagen Inc.
Disclosure
T. Bekaii-Saab: Financial Interests, Institutional, Research Grant: Agios, Arys, Arcus, Atreca, Boston Biomedical, Bayer, Eisai, Celgene, Lilly, Ipsen, Clovis, Seagen, Genentech, Novartis, Mirati, Merus, Abgenomics, Incyte, Pfizer; Financial Interests, Personal and Institutional, Advisory Board: Imugene, Immuneering, Xilis, Replimune , Sun Biopharma; Financial Interests, Personal and Institutional, Royalties: UpToDate. K. Lach: Financial Interests, Personal, Full or part-time Employment: Maple Health Group; Financial Interests, Personal and Institutional, Other, Paid consultant: Seagen. L. Hsu: Financial Interests, Personal, Full or part-time Employment: Seagen; Financial Interests, Personal, Stocks/Shares: Seagen. M.F. Siadak: Financial Interests, Personal, Full or part-time Employment: Seagen; Financial Interests, Personal, Stocks/Shares: Seagen. M. Stecher: Financial Interests, Personal, Full or part-time Employment: Seagen; Financial Interests, Personal, Stocks/Shares: Seagen. J. Ward: Financial Interests, Personal, Full or part-time Employment: Seagen; Financial Interests, Personal, Stocks/Shares: Seagen. R. Beckerman: Financial Interests, Personal, Full or part-time Employment: Maple Health Group; Financial Interests, Personal and Institutional, Other, Paid consultant: Seagen. J.H. Strickler: Financial Interests, Personal, Advisory Board: SeaGen, AstraZenca, Amgen, Pfizer, Bayer, Abbvie, Natera, Viatris, Inivata, Silverback Therapeutics; Financial Interests, Personal, Other, Consulting: Mereo, GSK, Pionyr Immunotherapeutics; Financial Interests, Institutional, Invited Speaker: SeaGen, Roche Genentech, Abbvie, AstraZeneca, Amgen, AStar D3, Sanofi, Curegenix, Nektar, Leap Therapeutics, Daiichi Sankyo, Erasca, Gossamer Bio, Silverback Therapeutics.