Abstract 487P
Background
HER2+ AGC treatment shows variable response to trastuzumab plus chemotherapy (T-CT), indicating the need for precise biomarkers. The HER2DX ERBB2 mRNA assay, a genomic test clinically validated in HER2+ breast cancer, offers a promising tool for enhancing patient selection for T-CT by quantifying ERBB2 mRNA expression levels.
Methods
This study utilized the standardized HER2DX ERBB2 mRNA assay to evaluate its association with survival outcomes and response rates in 60 patients with HER2+ AGC treated at 2 hospitals in Spain (H. Clinic Barcelona and H. General Granollers). HER2DX ERBB2 mRNA pre-established cutoffs were applied. A comparative analysis was conducted against conventional pathology-based HER2 immunohistochemistry (IHC) methods. The statistical approach included student´s t-test, Cox regression models adjusted for HER2 IHC groups and clinical variables, with Kaplan-Meier estimates for survival analysis, maintaining a significance level at p<0.05.
Results
Distribution among HER2DX ERBB2 low, medium, and high groups was 46.7%, 18.3%, and 35.0%, respectively. ERBB2 mRNA levels were distinct between HER2 IHC 2+ and 3+ categories (p<0.001) and were significantly higher in HER2+ breast cancer internal cohort than in HER2+ gastric cancer (p<0.001), even within the HER2 IHC 3+ subgroup (p<0.001). The HER2DX ERBB2 mRNA levels exhibited a significant association with progression-free survival (PFS), both as a continuous variable (hazard ratio [HR]=0.67, p=0.013). As a categorical variable, the high ERBB2 mRNA group showed a median PFS of 8.1 months compared to 3.0 months in the low ERBB2 mRNA group (HR=0.38, p=0.004). A similar significant association was found with overall survival (OS), where the HER2DX ERBB2 mRNA levels indicated better outcomes, with the high ERBB2 mRNA group achieving a median OS of 14.4 months compared to 7.0 months in the low group (HR=0.53, p=0.039). Results remained significant after adjusting for HER2 IHC, and other clinical variables.
Conclusions
The HER2DX ERBB2 mRNA assay demonstrates significant potential in refining patient selection for T-CT in HER2-positive AGC. Further research of the assay with novel anti-HER2 treatments seems warranted.
Legal entity responsible for the study
The authors.
Funding
SEOM.
Disclosure
T. Sauri Nadal: Financial Interests, Personal, Invited Speaker: BMS, MSD; Financial Interests, Personal, Advisory Board: Amgen. T. Pascual: Financial Interests, Personal, Invited Speaker: Pfizer/ AstraZeneca/Veracyte/Novartis; Financial Interests, Personal, Advisory Board: Roche/Genentech, Novartis. A. Prat: Financial Interests, Personal, Invited Speaker: Roche, 1TRIALSP, S.L.; Financial Interests, Personal, Invited Speaker, Lecture fees: Novartis, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Novartis, Pfizer, Peptomyc; Financial Interests, Institutional, Invited Speaker, Clinical trials: Daiichi Sankyo; Financial Interests, Institutional, Other, Contracted research: Boehringer Ingelheim, Medica Scientia Inno. Research; Financial Interests, Personal, Advisory Board: AstraZeneca, Reveal Genomics; Financial Interests, Personal, Member of Board of Directors, Leadership role: Reveal Genomics, SL.; Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Personal, Royalties: Reveal Genomics, International Oncology Bureau, S.L.; Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Novartis; Financial Interests, Personal and Institutional, Invited Speaker: Daiichi Sankyo; Financial Interests, Institutional, Funding: Reveal Genomics; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: Actitud Frente al Cáncer Foundation; Non-Financial Interests, Personal, Other, Asociación Española de Investigación sobre el Cáncer: ASEICA; Non-Financial Interests, Personal, Other, Research Foundation that gives grants to researchers: FERO. All other authors have declared no conflicts of interest.