PMID- 37805496
OWN - NLM
STAT- MEDLINE
DCOM- 20231009
LR  - 20231119
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 14
IP  - 1
DP  - 2023 Oct 7
TI  - Dalpiciclib and pyrotinib in women with HER2-positive advanced breast cancer: a 
      single-arm phase II trial.
PG  - 6272
LID - 10.1038/s41467-023-41955-7 [doi]
LID - 6272
AB  - CDK4/6 inhibitors have shown a synergistic effect with anti-HER2 therapy in 
      hormone receptor (HR)-positive and HER2-positive breast cancer (BC). In this 
      phase 2 study (NCT04293276), we aim to evaluate a dual-oral regimen of CDK4/6 
      inhibitor dalpiciclib combined with HER2 tyrosine kinase inhibitor pyrotinib as 
      front-line treatment in women with HER2-positive advanced BC (n = 41) including 
      those with HR-negative disease. The primary endpoint is the objective response 
      rate, and secondary endpoints include progression-free survival (PFS), overall 
      survival (OS), and safety. With a median follow-up of 25.9 months, 70% (28/40) of 
      assessable patients have a confirmed objective response, meeting the primary 
      endpoint. The median PFS is 11.0 months (95% CI = 7.3-19.3), and OS data are not 
      mature. The most common grade 3 or 4 treatment-related adverse events (AEs) are 
      decreased white blood cell count (68.3%), decreased neutrophil count (65.9%), and 
      diarrhea (22.0%). Most AEs are manageable, and no treatment-related deaths occur. 
      These findings suggest that this combination may have promising activity and 
      manageable toxicity. Further investigation is needed.
CI  - (c) 2023. Springer Nature Limited.
FAU - Yan, Min
AU  - Yan M
AUID- ORCID: 0000-0002-3911-748X
AD  - Department of Breast Disease, Henan Breast Cancer Center/The Affiliated Cancer 
      Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China. 
      ym200678@126.com.
FAU - Niu, Limin
AU  - Niu L
AD  - Department of Breast Disease, Henan Breast Cancer Center/The Affiliated Cancer 
      Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
FAU - Lv, Huimin
AU  - Lv H
AD  - Department of Breast Disease, Henan Breast Cancer Center/The Affiliated Cancer 
      Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
FAU - Zhang, Mengwei
AU  - Zhang M
AD  - Department of Breast Disease, Henan Breast Cancer Center/The Affiliated Cancer 
      Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
FAU - Wang, Jing
AU  - Wang J
AD  - Department of Breast Disease, Henan Breast Cancer Center/The Affiliated Cancer 
      Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
FAU - Liu, Zhenzhen
AU  - Liu Z
AUID- ORCID: 0000-0002-3878-1258
AD  - Department of Breast Disease, Henan Breast Cancer Center/The Affiliated Cancer 
      Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
FAU - Chen, Xiuchun
AU  - Chen X
AD  - Department of Breast Disease, Henan Breast Cancer Center/The Affiliated Cancer 
      Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
FAU - Lu, Zhenduo
AU  - Lu Z
AD  - Department of Breast Disease, Henan Breast Cancer Center/The Affiliated Cancer 
      Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
FAU - Zhang, Chongjian
AU  - Zhang C
AD  - Department of Breast Disease, Henan Breast Cancer Center/The Affiliated Cancer 
      Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
FAU - Zeng, Huiai
AU  - Zeng H
AD  - Department of Breast Disease, Henan Breast Cancer Center/The Affiliated Cancer 
      Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
FAU - Zhao, Shengnan
AU  - Zhao S
AD  - Department of Breast Disease, Henan Breast Cancer Center/The Affiliated Cancer 
      Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
FAU - Feng, Yajing
AU  - Feng Y
AD  - Department of Breast Disease, Henan Breast Cancer Center/The Affiliated Cancer 
      Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
FAU - Sun, Huihui
AU  - Sun H
AD  - Department of Breast Disease, Henan Breast Cancer Center/The Affiliated Cancer 
      Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
FAU - Li, Huajun
AU  - Li H
AD  - Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China.
LA  - eng
SI  - ClinicalTrials.gov/NCT04293276
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231007
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 5ZHA5P4PFX (dalpiciclib)
RN  - 0 (pyrotinib)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - 0 (Pyridines)
SB  - IM
MH  - Humans
MH  - Female
MH  - *Breast Neoplasms/drug therapy/genetics
MH  - Receptor, ErbB-2/metabolism
MH  - Pyridines/therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
PMC - PMC10560297
COIS- H.L. was an employee of Jiangsu Hengrui Pharmaceuticals Co., Ltd (Shanghai, 
      China) during the study period. The remaining authors have no conflicts of 
      interest to declare.
EDAT- 2023/10/08 02:42
MHDA- 2023/10/09 06:42
PMCR- 2023/10/07
CRDT- 2023/10/07 23:16
PHST- 2023/02/19 00:00 [received]
PHST- 2023/09/26 00:00 [accepted]
PHST- 2023/10/09 06:42 [medline]
PHST- 2023/10/08 02:42 [pubmed]
PHST- 2023/10/07 23:16 [entrez]
PHST- 2023/10/07 00:00 [pmc-release]
AID - 10.1038/s41467-023-41955-7 [pii]
AID - 41955 [pii]
AID - 10.1038/s41467-023-41955-7 [doi]
PST - epublish
SO  - Nat Commun. 2023 Oct 7;14(1):6272. doi: 10.1038/s41467-023-41955-7.