# Triple HER2 Blockade With Trastuzumab, Pertuzumab, and Pyrotinib Versus Dual HER2 Blockade in the Neoadjuvant Treatment of HER2‐Positive Breast Cancer: A Randomized, Phase II Study

## TL;DR

This study compared triple and dual HER2 treatments for breast cancer and found no improvement in outcomes with triple therapy, but more side effects.

## Contribution

The study is the first to evaluate triple HER2 blockade with pyrotinib in neoadjuvant breast cancer treatment.

## Key findings

- Triple HER2 blockade did not improve tpCR rates compared to dual blockade.
- Triple HER2 blockade was associated with higher toxicity, especially diarrhea.
- 65.5% tpCR rate was observed in the triple HER2 group versus 60.4% in the dual HER2 group.

## Abstract

This study aimed to evaluate the efficacy and safety of triple human epidermal growth factor receptor 2 (HER2) blockade with trastuzumab, pertuzumab, and pyrotinib (TPPy) versus dual HER2 blockade with trastuzumab and pertuzumab (TP) in the neoadjuvant treatment of HER2‐positive breast cancer. Patients with stage II–III HER2‐positive breast cancer were randomized (1:1) to receive TPPy or TP alongside weekly nab‐paclitaxel for 12 weeks. The primary endpoint was total pathological complete response (tpCR; ypT0/isN0). Exploratory biomarker and pathway analysis was done to identify patients benefiting from pyrotinib. A total of 109 patients were enrolled, and 108 received treatment: 55 in the TPPy group and 53 in the TP group. The tpCR rate was 65.5% (95% confidence interval [CI]: 51.4%–77.8%) in the TPPy group, and 60.4% (95% CI: 46.0%–73.5%) in the TP group (p = 0.585). In the TPPy group, 52 (94.5%) and 23 (41.8%) patients experienced dose interruption and discontinuation, respectively. The most common grade ≥3 adverse events in the TPPy and TP groups were diarrhea (58.1% vs. 0%) and neutropenia (23.6% vs. 15.1%). In conclusion, triple HER2 blockade did not improve tpCR rates compared with dual blockade but was associated with greater toxicity, particularly diarrhea.

Triple HER2 blockade with trastuzumab, pertuzumab, and pyrotinib (TPPy) did not improve total pathological complete response (tpCR) rates or breast pathological complete response (bpCR) rates compared with dual blockade with trastuzumab and pertuzumab (TP), but was associated with greater grade ≥ 3 toxicity, particularly diarrhea.