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In the front-line treatment of human epidermal growth factor receptor 2-positive patients, dalpiciclib with pyrotinib demonstrates promising efficacy and acceptable tolerability.

A highly selective, small-molecule CDK4/6 inhibitor, palbociclib (SHR6390), was recently authorized in China for hormone receptor (HR)-positive, human epidermal growth factor receptor (HER)2-negative advanced breast cancer (ABC). 

Pyrotinib is an orally administered, irreversible pan-ErbB receptor tyrosine kinase inhibitor (TKI) that targets HER1, HER2, and HER4. It works well and is approved for HER2-positive ABC in China. This study, published in the journal Nature Communications, investigated a dual-oral regimen of the CDK4/6 inhibitor dalpiciclib and the HER2 tyrosine kinase inhibitor pyrotinib as front-line therapy for 41 women with HER2-positive advanced BC, including HR-negative illness.

Study Population

The single-arm Phase II study ran from April 9, 2020 to May 19, 2021. This trial included women aged 18–70 with histologically proven advanced HER2-positive breast cancer who had received no more than one systemic treatment. For each 28-day cycle, all patients received pyrotinib 400 mg orally per day and palbociclib 125 mg orally per day for 21 days, followed by 7 days off.

Treatment Outcomes and Survival Rates

Twenty-eight participants had an objective response rate (ORR), with two complete and 26 partial responses. The predicted 12-month progression-free survival (PFS) was 44.7%, and the median PFS was 11 months. Overall survival (OS) rates were 90% and 82.5% at 12 and 18 months, respectively.

Safety Profile of Dalpiciclib and Pyrotinib

All 41 patients who received at least one dose of the study medication had at least one treatment-related adverse event (TRAE), and 34 (82.9%) and five (12.2%) had grade 3 and 4 TRAEs, respectively. Diarrhea (40/41, 97.6%), reduced white blood cell count (40/41, 97.6%), decreased neutrophil count (39/41, 95.1%), anemia (31/41, 75.6%), nausea (22/41, 53.7%), and stomatitis (21/41, 51.2%) were the most common. The Grade 3 TRAEs most often included reduced white blood cell count (28/41, 68.3%), reduced neutrophil count (22/41, 53.7%), diarrhea (9/41, 22.0%), and anemia (8/41, 19.5%). Grade 4 TRAE occurred in 12.2% of patients, all of whom experienced decreased neutrophil count.

Overall Response Rate and Progression-Free Survival in Brain Metastasis Patients
The baseline population included 13 individuals with asymptomatic brain metastasis (BM), 12 of whom had untreated BM. The overall response rate (ORR) for these 13 patients was 84.6%, and the central nervous system (CNS) response rate (CR) among those with detectable intracranial lesions was 66.7% (6/9). Overall, BM patients had a median PFS of 11 months.

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Patients with HER2-positive ABC now have another choice in the form of this entirely oral regimen. Additionally, this study may pave the way for future research into using CDK4/6 inhibitors in individuals with BC.


Yan, M., Niu, L., Lv, H., Zhang, M., Wang, J., Liu, Z., Chen, X., Lu, Z., Zhang, C., Zeng, H., Zhao, S., Feng, Y., Sun, H., & Li, H. (2023). Dalpiciclib and pyrotinib in women with HER2-positive advanced breast cancer: a single-arm phase II trial. Nature Communications, 14(1). https://doi.org/10.1038/s41467-023-41955-7