115P Neoadjuvant pyrotinib combined with trastuzumab, albumin paclitaxel, and carboplatin for HER2-positive early or locally advanced breast cancer: A single-arm phase II trial

In patients with HER2-positive metastatic breast cancer, pyrotinib (an irreversible pan-HER2 inhibitor) combined with chemotherapy shows survival benefits and acceptable tolerability. The trial aimed to assess the efficacy and safety of pyrotinib with trastuzumab, albumin paclitaxel, and carboplatin in the neoadjuvant setting (ChiCTR2100043523). In this single-arm phase II study, treatment-naive women with HER2-positive early or locally advanced breast cancer (II-III) were enrolled and received six neoadjuvant cycles of oral pyrotinib (400 mg) once daily, intravenous trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg), albumin paclitaxel (260 mg/m2), and carboplatin (area under the curve AUC = 6 mg/mL× min) every 3 weeks. The primary endpoint was the total pathological complete response (tpCR; ypT0/is and ypN0) rate. Secondary endpoints include objective response rate (ORR), disease control rate (DCR), breast pCR (bpCR; ypT0/is) rate, and safety. Between March 4, 2021, and August 25, 2023, 36 patients were enrolled, with a median age of 52 years (range, 29-63), 58.3% postmenopausal, 88.9% nodal involvement, and 63.9% stage III. The tpCR rate was 51.7% (95% CI 34.4% to 68.6%), and the bpCR was 58.6% (95% CI 40.7% to 74.5%). The ORR and DCR were 81.3% and 100.0% after two treatment cycles, 93.1% and 100.0% after four treatment cycles, and 100% and 100% after six treatment cycles, respectively. The most common grade 3 or 4 treatment-related adverse events included diarrhea (6 16.7%), vomiting (5 13.9%), decreased neutrophil count (4 11.1%), platelet count decrease (2 5.6%) and anemia (2 5.6%). No treatment-related deaths occurred, and no decrease in left ventricular ejection fraction was reported. Neoadjuvant pyrotinib in combination with trastuzumab, albumin paclitaxel, and carboplatin is an effective and safe treatment option for HER2-positive early or locally advanced breast cancer. The randomized controlled trial is necessary to validate our findings.