140MO - HER2DX genomic test in HER2-positive/hormone receptor-positive (HER2+/HR+) breast cancer (BC) treated with neoadjuvant trastuzumab (T) and pertuzumab (P): A correlative analysis from the PerELISA trial

Background

HER2DX is a prognostic and predictive assay in early-stage HER2+ BC based on clinical data and the expression of 4 gene signatures (immune, proliferation, luminal differentiation and HER2 amplicon), including ERBB2 levels. Here, we evaluated the ability of HER2DX to predict efficacy of a de-escalated, chemotherapy (CT)-free neoadjuvant regimen in HER2+/HR+ BC.

Methods

HER2DX was evaluated on pre-treatment FFPE tumor samples from the PerELISA phase II study for postmenopausal patients (pts) with operable HR+/HER2+ BC. Pts received 2-week (wk) letrozole (L), and then underwent re-biopsy for Ki67 evaluation. Patients with endocrine therapy sensitive tumors (EST) (i.e., >20% Ki67 relative reduction at wk 2) continued L and 5 cycles of trastuzumab T+P. Primary aim was to test the ability of HER2DX risk-score, HER2DX pCR score and HER2DX ERBB2 score (as continuous variables and group categories) to predict pathological complete response (pCR) in patients with EST. Logistic regression and receiver-operator curve (ROC) analysis assessed associations of HER2DX scores with 1) pCR and 2) EST.

Results

HER2DX was evaluated in 55 pts (86%) enrolled in PerELISA and 40 pts (73%) had EST. The pCR rate in pts with EST was 22.5% (9/40). In this group, HER2DX pCR score, but not HER2DX risk-score, was significantly associated with pCR (p=0.012; Area under ROC [AUC]=0.80). The pCR rate in low, medium, and high HER2DX pCR score groups was 8.0% (2/25), 43.0% (6/14) and 100.0% (1/1), respectively. HER2DX ERBB2 score was significantly associated with pCR (p=0.004; AUC=0.88) and independently of HER2 levels (2+ vs 3+). The pCR rate in low, medium, and high HER2DX ERBB2 score groups was 0.0% (0/12), 8.3% (1/12) and 50.0% (8/16), respectively. HER2DX pCR score was also significantly associated with Ki-67 response following 2-wk L (p=0.004; AUC=0.77). The rate of EST in low, medium, and high HER2DX pCR score groups was 89.3% (25/28), 66.7% (14/21) and 16.7% (1/6), respectively.

Conclusions

HER2DX predicts endocrine sensitivity and pCR following neoadjuvant T+P+letrozole in pts with early-stage HER2+/HR+ BC. HER2DX could help tailor systemic therapy in this context.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

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. 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. G. Griguolo: Financial Interests, Personal, Invited Speaker: Novartis, Eli Lilly; Other, Travel Support: Novartis, Amgen, Daiichi Sankyo; Other, Trave Support: Pfizer. L. Pare Brunet, M. Marin: Financial Interests, Full or part-time Employment: Reveal Genomics. F. Miglietta: Financial Interests, Invited Speaker: Roche. 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, Stocks/Shares: Reveal Genomics. J. Parker: Financial Interests, Stocks/Shares: Reveal Genomics. C.M. Perou: Financial Interests, Stocks/Shares: 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. All other authors have declared no conflicts of interest.