- Gastrointestinal cancer
-
Trastuzumab Combined with Irinotecan in Patients with HER2-Positive Metastatic Colorectal Cancer: A Phase II Single-Arm Study and Exploratory Biomarker Analysis
-
Ting Xu, Xicheng Wang, Ying Xin, Zhenghang Wang, Jifang Gong, Xiaotian Zhang, Yanyan Li, Congcong Ji, Yu Sun, Feilong Zhao, Depei Huang, Yuezong Bai, Jian Li, Lin Shen
-
Cancer Res Treat. 2023;55(2):626-635. Published online December 23, 2022
-
DOI: https://doi.org/10.4143/crt.2022.1058
-
-
 Abstract
 PDF Supplementary Material PubReader ePub
- Purpose
The human epidermal growth factor receptor 2 (HER2) is an established therapeutic target for various kinds of solid tumors. HER2 amplification occurs in approximately 1% to 6% of colorectal cancer. In this study, we aimed to assess the efficacy and safety of trastuzumab in combination with chemotherapy in HER2-positive metastatic colorectal cancer (mCRC).
Materials and Methods
An open-label, phase II trial (Clinicaltrials.gov: NCT03185988) was designed to evaluate the antitumor activity of trastuzumab and chemotherapy in HER2-positive digestive cancers excluding gastric cancer in 2017. Patients from this trial with HER2-positive, KRAS/BRAF wild-type, unresectable mCRC were analyzed in this manuscript. Eligible patients were treated with trastuzumab (8 mg/kg loading dose and then 6 mg/kg every 3 weeks) and irinotecan (120 mg/m2 days 1 and 8 every 3 weeks). The primary endpoint was the objective response rate.
Results
Twenty-one HER2-positive mCRC patients were enrolled in this study. Seven patients (33.3%) achieved an objective res-ponse, and 11 patients (52.4%) had stable disease as their best response. The median progression-free survival (PFS) was 4.3 months (95% confidence interval, 2.7 to 5.9). Four of the 21 patients (19.0%) had grade 3 adverse events, including leukopenia, neutropenia, urinary tract infection, and diarrhea. No treatment-related death was reported. Exploratory analyses revealed that high tumor tissue HER2 copy number was associated with better therapeutic response and PFS. Alterations in the mitogen-activated protein kinase pathway, HER2 gene, phosphoinositide 3-kinase/AKT pathway, and cell cycle control genes were potential drivers of trastuzumab resistance in mCRC.
Conclusion
Trastuzumab combined with chemotherapy is a potentially effective and well-tolerated therapeutic regimen in mCRC with a high HER2 copy number.
-
Citations
Citations to this article as recorded by  - Enhancing treatment strategies for small bowel cancer: a clinical review of targeted therapy and immunotherapy approaches
Mehrshad Ebrahimpour, Hamidreza Hosseinzadeh, Farshad Abedi, Mohammad Moeini Nodeh, Abolghasem Allahyari, Amirhossein Sahebkar, Omid Arasteh
Naunyn-Schmiedeberg's Archives of Pharmacology.2024; 397(7): 4601. CrossRef - Drug combinations of camptothecin derivatives promote the antitumor properties
Zhen Liu, Yajie Yuan, Ning Wang, Peng Yu, Yuou Teng
European Journal of Medicinal Chemistry.2024; 279: 116872. CrossRef - Functionalised Ligand-Based Nanomaterial Drug Targeting Approaches for Colorectal Cancer Therapy
Amol A. Dixit, Deepa S. Mandlik, Satish K. Mandlik
Recent Advances in Drug Delivery and Formulation.2024; 18(3): 170. CrossRef - Current Targeted Therapy for Metastatic Colorectal Cancer
Tomokazu Ohishi, Mika K. Kaneko, Yukihiro Yoshida, Atsuo Takashima, Yukinari Kato, Manabu Kawada
International Journal of Molecular Sciences.2023; 24(2): 1702. CrossRef - Immune Checkpoint Inhibitor-Based Combination Therapy for Colorectal Cancer: An Overview
Jingjing Li, Xuanfu Xu
International Journal of General Medicine.2023; Volume 16: 1527. CrossRef - Mechanism of multidrug resistance to chemotherapy mediated by P‑glycoprotein (Review)
Yichen Tian, Yongrong Lei, Yani Wang, Jiejuan Lai, Jianhua Wang, Feng Xia
International Journal of Oncology.2023;[Epub] CrossRef - Successful treatment with trastuzumab plus chemotherapy as the first‑line regimen in advanced small bowel adenocarcinoma harboring HER2 amplification: A report of two cases
Jingwen Wang, Xia Zhu, Jiayan Chen, Fei Liu, Xi Tang
Oncology Letters.2023;[Epub] CrossRef
-
5,259
View
-
201
Download
-
7
Web of Science
-
7
Crossref
|
KCA
