Case Report
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Sep 15, 2020; 12(9): 1065-1072
Published online Sep 15, 2020. doi: 10.4251/wjgo.v12.i9.1065
Response of human epidermal growth factor receptor 2-positive colorectal cancer to lapatinib monotherapy: A case report
Ji-Lin Guan, Jian-Hua Liu, Qing Wang, Yu-Wei Cong, Yao-Xu Chen, Ke-Fei Huang, Meng-Li Huang, Ling Huang
Ji-Lin Guan, Jian-Hua Liu, Ling Huang, Department of Oncology, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou 510655, Guangdong Province, China
Qing Wang, Yu-Wei Cong, Yao-Xu Chen, Meng-Li Huang, The Medical Department, 3D Medicines Inc., Shanghai 201114, China
Ke-Fei Huang, The Bioinformatic Department, 3D Medicines Inc., Shanghai 201114, China
Author contributions: Guan JL, Huang ML, and Huang L contributed to the case report design; Guan JL was the physician in charge who provided the patient’s information; Liu JH provided the histologic images, confirmed the diagnosis, and contributed the details about the histologic diagnosis; Wang Q collected and provided the data; Cong YW, Chen YX, and Huang KF performed NGS testing, formal analysis, and data visualization; Guan JL, Wang Q, and Chen YX were involved in writing, review, and editing of the manuscript; Huang L was the principle author of the paper, had full access to all data, and is the guarantor; Huang ML supervised the report and the publication process; all authors read and confirmed the final version of this article.
Informed consent statement: Written informed consent was obtained from the patient for publication of this case report and any accompanying images.
Conflict-of-interest statement: There is no conflict of interest to disclose.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Ling Huang, MD, Director, Doctor, Professor, Department of Oncology, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, No. 123 West Huifu Road, Yuexiu District, Guangzhou 510655, Guangdong Province, China. 13710351111@139.com
Received: April 22, 2020
Peer-review started: April 22, 2020
First decision: April 26, 2020
Revised: July 16, 2020
Accepted: August 16, 2020
Article in press: August 16, 2020
Published online: September 15, 2020
Processing time: 140 Days and 22.7 Hours
Abstract
BACKGROUND

Human epidermal growth factor receptor 2 (HER2) amplification is a molecular driver for a subset of colorectal cancers (CRCs) and one of the major causes of anti-epidermal growth factor receptor (EGFR) treatment failure. Compared to dual anti-HER2 treatments, which have been shown to be effective in HER2-positive metastatic CRC patients, single-agent anti-HER2 therapy is rarely used to treat CRC.

CASE SUMMARY

Herein, we report a case of RAS/BRAF-wild-type metastatic CRC that was identified as HER2-positive through circulating tumor DNA (ctDNA) testing by next-generation sequencing following the failure of two lines of therapy. Subsequently, the patient was given lapatinib monotherapy that led to a partial response with a progression-free survival of 7.9 mo. Moreover, serial ctDNA detection was used to monitor the efficacy of lapatinib. The aberration of HER2 copy number disappeared when radiographic assessment revealed a partial response. However, a high level of HER2 amplification was detected again at the time of disease progression. Finally, a phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha mutation was identified at the time of tumor progression, which may explain the acquired resistance to lapatinib.

CONCLUSION

This is the first case report of HER2-positive RAS/BRAF wild-type metastatic CRC patient responding to lapatinib monotherapy. It highlights that ctDNA testing is an effective and feasible approach to evaluate the efficacy of anti-HER2 therapy.

Keywords: Human epidermal growth factor receptor 2, Colorectal cancer, Lapatinib, Circulating tumor DNA, Case report

Core Tip: While dual anti-human epidermal growth factor receptor 2 (HER2) therapies are recommend as standard treatment for HER2-positive advanced colorectal cancer, anti-HER2 monotherapy is rarely used to treat this population. This case is the first report of a HER2-positive RAS/BRAF-wild-type metastatic colorectal cancer patient achieving a partial response following lapatinib monotherapy without serious adverse events. Next generation sequencing based circulating tumor DNA testing played an essential role in both treatment decision and efficacy/resistance monitoring.