Abstract 153P
Background
PREDICT is an online tool (https://breast.predict.nhs.uk/) designed to help make informed decisions about treatment following surgery for early invasive BC and estimates overall survival (OS). HER2DX is a prognostic test that integrates clinical data and gene expression from immune, proliferation, luminal differentiation and HER2 amplicon processes. Here, we explored the prognostic ability of HER2DX beyond the PREDICT tool.
Methods
HER2DX and PREDICT tool were evaluated on 427 FFPE surgical specimens from patients (pts) enrolled at Short-HER trial a phase III, multicentric study for pts with HER2+ BC. All pts received multi-agent chemotherapy (CT) and were randomized to 9 weeks of trastuzumab (T) or 1 year (y). PREDICT included all variables except for ki67 and mode of cancer detection. Distant metastasis-free survival (DMFS) and OS were evaluated. The median follow-up was 7.3 y. Survival Cox model likelihood ratios evaluated the contribution of each variable (i.e: HER2DX risk-score, HER2DX risk-score with biological variables-only (HER2DX-bio) and PREDICT 5-y and 10-y OS estimates).
Results
PREDICT tool 5-y and 10-y OS estimates were significantly associated with DMFS (p<0.001) and OS (p<0.001) in Short-HER. PREDICT 10-y OS provided more prognostic information for DMFS and OS than 5-y OS and was used for further analysis. Pts with a PREDICT 10-y OS of ≥90% (low-risk) represented 12% and the actual 8-y DMFS and 8-y OS were 98% and 100%, respectively. 88% of pts had a high risk with a PREDICT 10-y OS and the actual 8-y DMFS and 8-y OS were 84% and 89%, respectively. The concordance rate between PREDICT and HER2DX was 66%. PREDICT did not add significant prognostic information beyond HER2DX for DMFS (c2=2.5; p=0.118) but did for OS (c2=12.6; p<0.001), whereas HER2DX was the opposite (c2=18.4; p<0.001 for DMFS and c2=0.9; p=0.334 for OS). HER2DX-bio provided 21% of prognostic information obtained with combined HER2DX and PREDICT (c2=6.8; p=0.009).
Conclusions
HER2DX provides more DMFS information than PREDICT in early-stage HER2+ BC treated with adjuvant CT and T. PREDICT is a strong predictor of OS.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Reveal Genomics, S.L.
Funding
Has not received any funding.
Disclosure
L. Pare Brunet: Financial Interests, Full or part-time Employment: Reveal Genomics, S.L. F. Brasó-Maristany: Financial Interests, Personal, Invited Speaker: Reveal Genomics. 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. M.V. Dieci: Financial Interests, Personal, Invited Speaker: Eli Lilly, Pfizer; Financial Interests, Personal, Advisory Board: Novartis, Eli Lilly, Seagen, Exact Science; Financial Interests, Personal, Other, Consultancy: Pfizer; Financial Interests, Institutional, Research Grant: Veneto Institute of Oncology IOV-IRCCS, Italian Ministry of health, University of Padova. M. Marin: Financial Interests, Full or part-time Employment: Reveal Genomics. V. Guarneri: Financial Interests, Personal, Advisory Board: Roche, Eli Lilly, Novartis, MSD, Gilead; Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis; Financial Interests, Institutional, Invited Speaker: Eli Lilly, Roche, BMS, Novartis, AstraZeneca, MSD, Synton Biopharmaceuticals, Merck. 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, Full or part-time Employment: Reveal Genomics, S.L; Financial Interests, Other, Equity stock holder and consultant of Reveal Genomics: Reveal Genomics, S.L. J. Parker: Financial Interests, Other, Equity stock holder and consultant of Reveal Genomics: Reveal Genomics, S.L. C.M. Perou: Financial Interests, Other, Equity stock holder and consultant of Reveal Genomics: Reveal Genomics, S.L. 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, BMS, Puma, Oncolytics Biotech, MSD, 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. All other authors have declared no conflicts of interest.