149P - Assessing the effect of single dose trastuzumab and pertuzumab (HP) on biological changes and pathological complete response (pCR) in ERBB2+ Breast Cancer: Results from the neoadjuvant BionHER study

Background

HER2 blockade in ERBB2+ BC can boost the immune system and inhibit cell proliferation and survival. Here, we aimed to identify early molecular changes following a single dose of HP and its association with subsequent pCR following neoadjuvant HP-based chemotherapy.

Methods

Patients (pts) with stage I-III ERBB2+BC were treated with neoadjuvant pertuzumab+trastuzumab+paclitaxel (THP)x16w. Paired tumor biopsies were obtained at baseline (D1) and at day 8 (D8) following a loading-dose of HP, prior to weekly paclitaxel addition. HER2DX gene expression signatures and the expression of 185 genes were evaluated in both timepoints. Paired SAM analyses (FDR<5%) and t-tests determined significant changes between D1-D8. Logistic regression analyses identified associations with pCR (ypT0/isN0).

Results

Gene expression was evaluated in paired samples in 49 out of 52 pts (94%). cT1-2 disease represented 85% of cases, cN0 59%, and 67% were HR+. The overall pCR rate was 45.6% and 55.3% when ypT1miN0 was considered. In all pts, HP induced a significant decrease in HER2DX proliferation, HER2 amplicon, pCR, risk and ERBB2 scores, and in 81 (43.8%) genes including KRT18, SPDEF, MUCL1 or FOXA1; and a significant increase in the HER2DX IGG signature and 84 (45.4%) genes including GPNMB, CD68, CD86 or CD4. At D8, the HER2DX IGG signature (p=0.002) and 61 (33.0%) genes including LY9 (p<0.001), CD8A (p<0.001), CD27 (p<0.001) or GZMA (p<0.001) were significantly associated with pCR. At D1, pCR rates in HER2DX IGG-high, medium and low were 71.4%, 22.2% and 25.0%, respectively. At D8, pCR rates in HER2DX IGG-high, medium and low were 81.0%, 33.3% and 6.3%, respectively. The ratio between D8 and D1 of HER2DX pCR (p=0.006) and risk (p=0.026) scores and 38 (20.5%) genes including S100A9 (p=0.006), TRPV6 (p=0.008), GPNMB (p=0.013) or LY9 (p=0.016) were significantly associated with pCR.

Conclusions

In early-stage ERBB2+ BC, a single dose of HP induces significant biological changes that may better predict pCR. At day 8, pts with high expression of HER2DX immune signature and immune-related genes have a higher probability of achieving a pCR following THP.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Reveal Genomics S.L.

Disclosure

All authors have declared no conflicts of interest.