- 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  - HER2-targeted therapy in colorectal cancer: a comprehensive review
Yeliz Benli, Helin Arıkan, Özge Akbulut-Çalışkan
Clinical and Translational Oncology.2025;[Epub] CrossRef - Disintegration of the KITENIN/ErbB4 Functional Complex by the Flavonoid Hispidulin Suppresses Colorectal Cancer Progression
Mücahit Varlı, Songjin Oh, Eunae Kim, Barış Gökalsın, Nüzhet Cenk Sesal, Kyung Keun Kim, Man Jeong Paik, Hangun Kim
Advanced Therapeutics.2025;[Epub] CrossRef - 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 - Nimotuzumab and irinotecan synergistically induce ROS‐mediated apoptosis by endoplasmic reticulum stress and mitochondrial‐mediated pathway in cervical cancer
Fei Teng, Lujun Zhao
Biotechnology and Applied Biochemistry.2024;[Epub] 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
-
6,353
View
-
212
Download
-
10
Web of Science
-
10
Crossref
|
KCA
