224P - Neoadjuvant pyrotinib plus trastuzumab, docetaxel, and carboplatin in patients with HER2-positive early breast cancer: A single-group, multicenter, phase II study

Background

Pyrotinib is a new oral, irreversible pan-ErbB receptor tyrosine kinase inhibitor that targets human epidermal growth factor receptor 1 (HER1), HER2, and HER4. Previous studies have confirmed that progression-free survival (PFS) is safe and well-tolerated in advanced breast cancer. However, the efficacy of pyrotinib plus trastuzumab-based dual HER2 blockade in neoadjuvant therapy for early breast cancer is unknown. The present study aimed to explore the efficacy of pyrotinib in neoadjuvant therapy for early breast cancer.

Methods

This single-group, multicenter, open-label, investigator-initiated phase II study recruited eligible patients, aged 18–70 years with invasive carcinoma, cT_2-3N_0-3M0 stage, HER2-positive breast cancer. The patients received 320 mg pyrotinib orally once per day for 21 days plus standard chemotherapy (pyrotinib+TCH) with six 21-day cycles of docetaxel (75 mg/m²) plus carboplatin (6 mg/mL/min) and trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance dose). The primary endpoint was to calculate the number of patients who achieved a pathological complete response (pCR, ypT0/is, ypN0). Simon^,s two-stage design with a two-sided α error of 5% and a power of 80% was applied for statistical evaluation; the expected pCR rate was 56%. A total of 75 samples was required for the study with a drop rate of 10%; of these, 31 evaluable patients were to be treated in the first stage, and at least 12 patients with pCR were required to continue to the second stage (NCT03735966).

Results

The results of the first 31 patients were reported. The pCR of 16 (51.6%) patients, who reached the threshold for the design, was noted. The study is ongoing. The most frequent grade 3 to 4 adverse events were diarrhea (58.1%), anemia (45.2%), and vomiting (16.1%). However, no treatment-related deaths were recorded.

Conclusions

The current trial suggests that pyrotinib plus trastuzumab-based standard chemotherapy has promising efficacy and manageable toxicity in patients with HER2-positive early breast cancer in a neoadjuvant setting, and phase III trials are warranted.

Clinical trial identification

NCT03735966.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.