Efficacy and safety of neoadjuvant treatment of trastuzumab and pyrotinib plus dalpiciclib in HR-negative/HER2-positive breast cancer: an exploratory, open-label phase II study

Background: To evaluate the efficacy and safety of a chemotherapy-free regimen consisting of monoclonal antibody trastuzumab, tyrosine kinase inhibitor pyrotinib and CDK4/6 inhibitor dalpiciclib in patients with hormone receptor-negative/HER2-positive (HR-HER2 +) early breast cancer (EBC). Materials and Methods: This open-label, single-arm, phase II study was designed using the Simon two-stage method (Chi-CTR-2 200 060 748). Patients with operable HR-HER2 + EBC (T1-3 and N0-2) were enrolled. Eligible patients received trastuzumab (HLX02, 8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks intravenously), pyrotinib (400 mg daily orally) and dalpiciclib (125 mg daily orally for 3 weeks, followed by 1 week off) for 16 weeks. Surgery was performed 3-6 weeks after the completion of drug treatment. The primary endpoint was total pathological complete response (tpCR, ypT0/Tis, ypN0) rates at surgery, and secondary endpoints included breast pCR (bpCR) rates (ypT0/Tis), residual cancer burden (RCB), objective response rate (ORR), change of Ki-67 scores, survival and safety. Results: Between Jun, 2022, and Jun, 2024, a total of 34 patients with a median age of 55 years (range: 35-67) were enrolled. 30 patients received all cycles of treatment and underwent surgery with a median follow-up of 20 months. The tpCR was achieved in 19 patients (63.3%; 95% CI, 45.5-78.1%). The bpCR was 66.7% (20/30). The number of patients with RCB-0 or RCB-I was 22 (73.3%). The most common Grade 3 treatment-related adverse events were diarrhea (50.0%), neutropenia (20.6%), and leukopenia (17.7%). No Grade 4 events or treatment-related deaths occurred. Conclusion: In patients with HR-HER2 + EBC, the neoadjuvant therapy with trastuzumab, pyrotinib and dalpiciclib has promising activity and manageable toxicity. Further investigation is needed.