1MO - HER2DX assay and survival outcomes: An individual-patient level meta-analysis of 2,031 patients with HER2-positive breast cancer

Background

The 27-gene HER2DX test predicts pathological complete response (pCR) following neoadjuvant trastuzumab-based chemotherapy for HER2-positive (HER2+) breast cancer. Furthermore, HER2DX was associated with survival outcomes across individual studies using different treatment strategies. Here, we combine the existing data to evaluate the prognostic capacity of HER2DX to predict survival outcomes.

Methods

We conducted an individual-patient level meta-analysis of seven cohorts including 2,031 patients with early-stage HER2+ breast cancer with HER2DX, clinical and efficacy data (SCAN-B [n=757], APT [n=284], PHERGain [n=272], CALGB40601 [n=263], ATEMPT [n=187], NEOHER [n=184], and PAMELA [n=84]). HER2DX risk score was evaluated i) as continuous score (from 0 to 100) and ii) as a risk group using pre-established cut-offs [low [0, 50) and high [50,100)]. The primary endpoint of the study was event-free survival (EFS). The Kaplan-Meier method was used to estimate survival outcomes and the stratified Cox model was performed to calculate hazard ratios (HRs).

Results

The overall median follow-up was 6.4 years, 52.4% of patients were classified into the HER2DX low-risk category and 47.6% as high-risk. In the multivariable analysis, HER2DX risk-score as a continuous variable was statistically associated with EFS after adjustment by study and clinical-pathological variables (HR per 10-units increment= 1.29, 95% CI 1.16-1.42; p<0.001). The 6-years EFS was 93.0% for the HER2DX low-risk and 82.9% and for the HER2DX high-risk (HR=2.25, 95% CI 1.43-3.54; p=0.001). The association remained consistent across all subgroups, regardless of tumor and nodal stage, pCR, and hormone receptor status (Table). Table: 1MO

Conclusions

In patients with early-stage HER2+ breast cancer, HER2DX provides prognostic information on long-term outcomes beyond clinical-pathological variables and pCR status.

Legal entity responsible for the study

The authors.

Funding

Reveal Genomics.

Disclosure

G. Villacampa Javierre: 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 Fabre, 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. J. Cortés: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Lilly, MSD, LEUKO, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics, Jazz Pharmaceuticals, AbbVie, Scorpion Therapeutics, Biocon; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Eisai, Pfizer, Lilly, MSD, Daiichi Sankyo; Financial Interests, Personal, Other, Consulting/advisor: Expres2ion Biotechnologies; Financial Interests, Personal, Other, consulting: Bridgebio; Financial Interests, Personal, Stocks/Shares: MAJ3 Capital; Financial Interests, Personal, Stocks/Shares, (relative): Leuko; Financial Interests, Institutional, Research Grant: Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, Guardan health, MSD, Pfizer, Piqur Therapeutics, Queen Mary University of London; Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo, Pfizer, Gilead, AstraZeneca, Stemline Therapeutics; Other, travel cost and expenses: MSD. J.M. Pérez García: Financial Interests, Member: MEDSIR. A. Llombart Cussac: Financial Interests, Research Grant: Roche, Agendia, Eli Lilly & Company, Pfizer, Novartis, Merck Sharp & Dohme, Gilead, Daiichi-Sanyo; Financial Interests, Speaker’s Bureau: Bristol-Myers, Genentech, Lilly, Roche, Pfizer, Novartis; Financial Interests, Funding: AstraZeneca; Financial Interests, Ownership Interest: MedSIR, Initia-Research. P. Tarantino: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, AstraZeneca, Daiichi Sankyo, Genentech, Eli Lilly, Gilead; Financial Interests, Institutional, Funding: AstraZeneca. P.F. Conte: Financial Interests, Personal, Advisory Board, advisory board for alpelisb trial: Novartis; Financial Interests, Institutional, Research Grant: Merck Kga; Non-Financial Interests, Advisory Role, Chairman of EDMC of two trials: Pfizer. M. Mancino: Financial Interests, Member: MEDSIR. V. Guarneri: Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, GSK, AstraZeneca, Gilead, Exact Sciences; Financial Interests, Personal, Advisory Board: Eli Lilly, Novartis, MSD, Gilead, Merck, Exact Sciences, Eisai, Olema Oncology, AstraZeneca, Daiichi Sankyo, Pfizer; Financial Interests, Personal, Expert Testimony: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Eli Lilly, Roche, BMS, Novartis, AstraZeneca, MSD, Synton Biopharmaceuticals, Merck, GSK, Daiichi Sankyo, Nerviano, Pfizer; Non-Financial Interests, Member: ASCO. M.V. Dieci: Financial Interests, Personal, Invited Speaker: Eli Lilly, Exact sciences, Gilead, Seagen, Daiichi Sankyo, Novartis; Financial Interests, Personal, Advisory Board: Novartis, Eli Lilly, Seagen, Exact Science, Daiichi Sankyo, Gilead; Financial Interests, Personal, Other, Consultancy: Pfizer; Financial Interests, Personal, Other, Consultancy on educational project: Roche. A. Waks: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Genentech, Macrogenics, Merck, Gilead. F. Brasó-Maristany: Financial Interests, Personal, Full or part-time Employment, part time employment: Reveal Genomics SL; Financial Interests, Personal, Other, Patents filed: EP23382703 and EP23383369: Reveal Genomics SL; Financial Interests, Personal, Other, Patents filed: PCT/EP2022/086493, PCT/EP2023/060810: Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer. T. Pascual: Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Veracyte, Novartis; Financial Interests, Personal, Advisory Board: Roche/Genentech, Novartis. G. Griguolo: Financial Interests, Personal, Invited Speaker: Novartis, Eli Lilly, MSD; Financial Interests, Personal, Advisory Board: Gilead, Menarini, Seagen; Other, Travel Support: Novartis, Amgen, Daiichi Sankyo, Eli Lilly, Gilead; Other, Trave Support: Pfizer. P. Villagrasa Gonzalez: Financial Interests, Personal, Full or part-time Employment, CEO and co-founder of the company: Reveal Genomics S.L.; Financial Interests, Personal, Ownership Interest: Reveal Genomics S.L.; Financial Interests, Personal, Royalties, PCT/EP2021/086493 - IN vitro method for the prognosis of patients suffering from HER2-positive breast cancer: Reveal Genomics S.L. J. Parker: Financial Interests, Personal, Other, Advisory: Reveal Genomics, Bristol Myers Squibb; Financial Interests, Personal, Full or part-time Employment: LifeEdit Therapeutics; Financial Interests, Personal, Ownership Interest: Reveal Genomics, GeneCentric; Financial Interests, Personal, Royalties: Veracyte. A. Vivancos: Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, Guardant Health, Bayer, Incyte; Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Bristol Myers Squibb, Roche, Incyte. C.M. Perou: Financial Interests, Personal, Other, consultant: GeneCentric Therapeutics, Bioclassifier LLC, Reveal Genomics; Financial Interests, Personal, Member of Board of Directors: GeneCentric Therapeutics; Financial Interests, Personal, Ownership Interest: GeneCentric Therapeutics, Bioclassifier LLC, Reveal Genomics; Financial Interests, Personal, Royalties: Bioclassifier LLC. 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: SOLTI; Financial Interests, Institutional, Other, Patent filed: EP23382703: Reveal Genomics S.L.; Financial Interests, Institutional, Other, Patent filed: EP23383369: Reveal Genomics S.L. 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. S.M. Tolaney: Financial Interests, Personal, Advisory Board, Ad board participant/consultant: ARC Therapeutics, Daiichi Sankyo, Eisai, Genentech/Roche, Gilead, Novartis, Sanofi, Seagen; Financial Interests, Personal, Other, Consulting: Aadi BioPharma; Financial Interests, Personal, Advisory Board, Ad board participation: Artios, Incyte Corp, Beyond Springs; Financial Interests, Personal, Advisory Board, Ad Board Participant/Consultant: AstraZeneca, Eli Lilly; Financial Interests, Personal, Advisory Board, Advisory Board participation: Bayer, Infinity Therapeutics, Myovant, OncXerna, Umoja Biopharma, Zentalis, Zetagen, Natera; Financial Interests, Personal, Other, Consultant: Blueprint Medicines; Financial Interests, Personal, Advisory Board, Ad board participant: Bristol Myers Squibb, Mersana Therapeutics; Financial Interests, Personal, Other, Steering Committee Member/Consultant: CytomX; Financial Interests, Personal, Advisory Board, Advisory Board participation/consulting: Menarini/Stemline; Financial Interests, Personal, Advisory Board, Ad Board participant/consultant: Merck; Financial Interests, Personal, Advisory Board, Ad board participant/Consultant: Pfizer; Financial Interests, Personal, Advisory Board, Advisory board participation: Reveal Genomics; Financial Interests, Personal, Advisory Board, Advisory Board Participation: Zymeworks; Financial Interests, Personal, Advisory Board, Advisory board/consulting: Jazz Pharma; Financial Interests, Institutional, Funding, And steering committing: AstraZeneca; Financial Interests, Institutional, Funding, And steering committee: Eli Lilly; Financial Interests, Institutional, Funding: Pfizer, Sanofi, Seagen, Odonate, Cyclacel, Exelixis, Bristol Myers Squibb, Eisai, Merck, Novartis; Financial Interests, Personal and Institutional, Invited Speaker: CytomX; Financial Interests, Institutional, Funding, and steering committee: Gilead, Genentech/Roche; Financial Interests, Institutional, Invited Speaker: Stemline/Menarini.