Abstract 237P
Background
The value of the HER2DX genomic assay in patients with advanced HER2+ disease is currently unknown. Here, we evaluated the association of the information provided by the HER2DX assay with T-DM1 benefit and survival.
Methods
HER2DX assay measures the expression of 4 biological processes (immune, proliferation, luminal differentiation and HER2 amplicon), including the levels of ERBB2. HER2DX is prognostic in early-stage HER2+ breast cancer. Here, we evaluated HER2DX in FFPE tumor samples from 76 consecutive patients treated with T-DM1 monotherapy in advanced HER2+ breast cancer at Hospital Clinic of Barcelona (Spain) and the University of Padova (Italy). Each HER2DX gene (n=27) and signature (n=6) was associated with T-DM1 response (complete/partial response versus stable/progressive disease) using logistic regression analysis (and ROC AUC). Progression-free survival (PFS) and overall survival (OS) were evaluated using Cox model analysis. Adjustment for clinical-pathological variables, including HER2 IHC expression, was also performed.
Results
A total of 76 tumor samples (51% archival primary tumors and 49% metastatic tumors) were included. Most patients (n=61, 80%) were treated in 2nd/3rd-line for advanced disease. The overall response rate (ORR), median PFS and median OS were 46.1%, 5.3 months and 12.2 months, respectively. Among all variables, ERBB2 mRNA expression was significantly associated with ORR, PFS and OS. According to the pre-specified cutoffs, the ORR in ERBB2 low, medium, and high groups was 0%, 28.6% and 57.4%, respectively (p<0.001; AUC=0.72). ERBB2 mRNA was also significantly associated with better PFS (Hazard Ratio [HR]=0.73, p=0.032) and better OS (HR=0.69, p=0.038). These findings were found irrespective of HER2 IHC levels (2+ vs. 3+), hormone receptor status and line of therapy. Among the other variables analyzed, the IGG/immune signature was found significantly associated with better OS (HR=0.59, p=0.001) in all patients, and in patients treated in 2nd/3rd-line (HR=0.51, p=0.003).
Conclusions
HER2DX assay provides prognostic and predictive information following T-DM1 in advanced HER2+ breast cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
F. Brasó-Maristany: Financial Interests, Personal, Invited Speaker: Reveal Genomics. G. Griguolo: Financial Interests, Personal, Invited Speaker: Novartis, Eli Lilly; Other, Other, Travel Support: Novartis, Amgen, Daiichi Sankyo; Other, Other, Trave Support: Pfizer. L. Pare Brunet: Financial Interests, Full or part-time Employment: 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. F. Miglietta: Financial Interests, Invited Speaker: Roche. M. Marin: Financial Interests, Personal, Full or part-time Employment: Reveal Genomics. 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, Stocks/Shares: Reveal Genomics. J. Parker: Financial Interests, Personal, Stocks/Shares, equity stock holder and consultant: Reveal Genomics. C.M. Perou: Financial Interests, Personal, Stocks/Shares, equity stock holder and consultant: Reveal Genomics. 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. V. Guarneri: Financial Interests, Personal, Advisory Board: Roche, EliLilly, Novartis, MSD, Gilead; Financial Interests, Personal, Invited Speaker: EliLilly, Novartis; Financial Interests, Institutional, Invited Speaker: EliLilly, Roche, BMS, Novartis, AstraZeneca, MSD, Synton Biopharmaceuticals, Merck. All other authors have declared no conflicts of interest.