Abstract 5P
Background
The risk-score of the HER2DX genomic test (HER2DX risk-score) was first validated in an independent combined dataset of 268 patients (pts) with early-stage HER2+ breast cancer treated with neoadjuvant and adjuvant anti-HER2-based treatment (EBioMedicine 2022). Here, we report an updated survival analysis with longer follow-up, with a special focus on the value of HER2DX risk-score beyond pathological complete response (pCR).
Methods
A dataset of 268 pts with early-stage HER2+ disease obtained from a combined cohort of 3 neoadjuvant studies was used for an independent validation of the standardized HER2DX risk-score. The dataset was composed of 147 pts from Hospital Clinic, 84 pts from PAMELA trial and 37 pts from the Padova University cohort. All pts received chemotherapy and 1-year of trastuzumab; 56% of pts received dual HER2 blockade; and 9% pts with residual disease received adjuvant T-DM1. The Kaplan-Meier method and stratified Cox models were used to estimate hazard ratios (HRs) to evaluate the association between HER2DX and disease-free survival (DFS).
Results
Median follow-up was 73.2 months (vs. 52.7 months in the prior report). HER2DX score as a continuous variable was significantly associated with DFS (HR=1.97, p=0.003) and overall survival (HR=2.23, p=0.009). According to the prespecified cut-off, the HER2DX low-risk group had longer DFS than high-risk (7-year 94.6% vs. 77.5%; HR=0.4, p=0.002). HER2DX risk-score was significantly (HR=1.90; p=0.003) associated with DFS independently of pCR status and hormone receptor status. Within pts with a pCR (n=118), the HER2DX low-risk group had longer DFS than the high-risk (5-year 96.5% vs. 88.4%; HR=0.33, p=0.178). Within pts without a pCR (n=148), the HER2DX low-risk group had longer DFS than the high-risk (5-year 95.6% vs. 85.3%; HR=0.20, p=0.004), and it was significantly (HR=2.03; p=0.006) associated with DFS independently of hormone receptor and adjuvant T-DM1.
Conclusions
The HER2DX risk-score determined in baseline pre-treatment core-biopsies provides prognostic information beyond pCR status in patients with early-stage HER2+ breast cancer treated with neoadjuvant and adjuvant anti-HER2 treatment.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
O. Martinez Saez: Financial Interests, Personal, Invited Speaker: Novartis, Eisai; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Other, Travel expenses: Roche; Financial Interests, Personal, Other, Medical advisory: Reveal Genomics. F. Brasó-Maristany: Financial Interests, Personal, Invited Speaker: Reveal Genomics. L. Pare Brunet: Financial Interests, Institutional, Full or part-time Employment: Reveal Genomics S.L.; Financial Interests, Institutional, Other, Patent pending: In vitro method for the prognosis of patients suffering from HER2-positive breast cancer - 905333: Reveal Genomics S.L. J. Cortés: Financial Interests, Personal, Advisory Board: Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, MERCK SHARP& DOHME, GSK, LEUKO, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp& Dohme, Daiichi Sankyo; Financial Interests, Personal, Other, Consulting/advisor: Expres2ion Biotechnologies; Financial Interests, Personal, Stocks/Shares: MedSIR, Nektar Therapeutics; Financial Interests, Institutional, Research Grant: Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma B, Queen Mary University of London; Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo, Pfizer, Gilead, AstraZeneca. G. Villacampa: Financial Interests, Personal, Invited Speaker, Invited speaker in a course: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker, Invited speaker in an internal training: Pierre Fabrer, GSK; Financial Interests, Personal, Invited Speaker, Internal discussion about the interpretation of some published results: Pfizer; Financial Interests, Personal, Other, Collaborations with specific projects: Reveal Genomics. M. Marín-Aguilera: Financial Interests, Institutional, Full or part-time Employment, Product Manager: Reveal Genomics, S.L. M. Munoz: Financial Interests, Personal, Expert Testimony: Roche, Novartis; Financial Interests, Personal, Other, International conference travel grants: Roche, Pfizer, Lilly, Gilead; Financial Interests, Personal, Advisory Board: Pierre Fabre, Seagen, AstraZeneca. A. Vivancos: Financial Interests, Personal, Advisory Board: Roche, Bristol Meyers Squibb, Guardant Health, Bayer, Incyte; Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Bristol Meyers Squibb, Roche, Incyte. P. Villagrasa Gonzalez: Financial Interests, Personal and Institutional, Member of the Board of Directors: Reveal Genomics; Financial Interests, Personal and Institutional, Proprietary Information: Reveal Genomics. P.F. Conte: Financial Interests, Personal, Advisory Board, advisory board for alpelisb trial: Novartis; Financial Interests, Institutional, Research Grant: Merck KGaA. A. Prat: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker, Lecture fees: Novartis, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Novartis, Pfizer, Oncolytics Biotech, Guardant Health, Peptomyc; Financial Interests, Institutional, Invited Speaker, Clinical trials: Daiichi Sankyo; Financial Interests, Institutional, Other, Contracted research: Boehringer, Medica Scientia inno. Research; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker, Leadership role: Reveal Genomics, SL.; Financial Interests, Personal, Stocks/Shares: Reveal Genomics, Oncolytics Biotech; Financial Interests, Personal, Royalties: Reveal Genomics; Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Novartis; Financial Interests, Personal and Institutional, Invited Speaker: Daiichi Sankyo; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: SOLTI Foundation, Actitud Frente al Cáncer Foundation; Non-Financial Interests, Personal, Other, Asociación Española de Investigación sobre el Cáncer: ASEICA.T. Pascual: Financial Interests, Personal, Invited Speaker: Pfizer/ AstraZeneca / Veracyte / Novartis; Financial Interests, Personal, Advisory Board: Roche/Genentech. V. Guarneri: Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, Amgen, GSK; Financial Interests, Personal, Advisory Board: Eli Lilly, Novartis, MSD, Gilead, Sanofi, Merck Serono, Exact Sciences, Eisai, Olema Oncology; Financial Interests, Personal, Expert Testimony: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Eli Lilly, Roche, BMS, Novartis, AstraZeneca, MSD, Synton Biopharmaceuticals, Merck, GlaxoSmithKline, Daiichi Sankyo, Nerviano; Non-Financial Interests, Member: ASCO. All other authors have declared no conflicts of interest.