2461 - Lack of benefit of neoadjuvant pertuzumab in high risk HER2 positive breast cancer. A retrospective case-control study of 355 cases with biomarker analysis.

Background

The NEOSPHERE trial suggested that pertuzumab (P) added to a combination of docetaxel and trastuzumab (T) as a neoadjuvant therapy in HER2 positive breast cancer (HER2+ BC) patients (pts) significantly enhances pathological complete response (pCR) rates. Here, we report our institution experience, focusing on stage III tumors.

Methods

We reviewed clinical and pathological response (residual cancer burden, RCB) in 355 HER2+ BC treated between 2010 and 2017 with neoadjuvant chemotherapy combined with T (n = 291) or TP (n = 64). Results were adjusted according to clinical stage, hormone receptors (HR) status, and chemotherapy regimen. In a subset of 157 pts matched on clinical TNM stage and HR expression (T, n = 98; TP, n = 59), a baseline pathological biomarker analysis was performed to assess TILs, PTEN, FOXP3 and PD-L1 expression.

Results

Among 355 patients, tumor clinical stages were T3 -T4 for 40% vs. 72% of T and TP pts (p < 0.0001). HR were expressed in 40% of T group and 22% of TP group (p = 0.002). Most tumors were grade 3 (63% in both groups). Almost all pts received taxanes, and 81% (T) vs. 69% (TP) received anthracyclines (p = 0.03). Breast conserving surgery (BCS) was performed in 52% (T) and 34% (TP) of pts (p = 0.008). pCR (RCB=0) was observed in 43% and 51% of T and TP groups, respectively (p = 0.25). For stage III pts, pCR was achieved in 48% (T) and 53% (TP) of pts (p = 0.25). Multivariate analyses did not show any independent factor associated with pCR. Features of the biomarker subset were similar among both groups: stage III=81%; HR negative=70%; grade 3=63%; anthracyclines 79% (T) and 68% (p = 0.09); BCS=31%. RCB=0 was seen in 50% (T) and 53% (TP) of pts (p = 0.93). Immune cells infiltration (CD8+, PD-L1+ and FOXP3+ lymphocytes) and tumor PD-L1 expression rates were higher in TP group (p < 0.0001). None of the pathological biomarkers correlated with pathological response.

Conclusions

This retrospective study did not suggest any benefit of neoadjuvant TP dual HER2 blockade regarding pathological response for stage III HER2+ BC. Baseline pathological expressions of PTEN, FOXP3, TILs, PD-L1 did not correlate with pathological response.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Institut Curie.

Funding

Institut Curie.

Disclosure

All authors have declared no conflicts of interest.