Sasaki M, Shimura T, Nishie H, Kuroyanagi K, Kanno T, Fukusada S, Sugimura N, Mizuno Y, Nukui T, Uno K, Kojima Y, Nishigaki R, Tanaka M, Ozeki K, Kubota E, Kataoka H. BRAF K601E-mutated metastatic colorectal cancer in response to combination therapy with encorafenib, binimetinib, and cetuximab: A case report. World J Gastrointest Oncol 2024; 16(7): 3357-3363 [PMID: 39072179 DOI: 10.4251/wjgo.v16.i7.3357]
Corresponding Author of This Article
Takaya Shimura, MD, PhD, Associate Professor, Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Science, 1 Kawasumi, Mizuho, Nagoya 467-8601, Japan. tshimura@med.nagoya-cu.ac.jp
Research Domain of This Article
Oncology
Article-Type of This Article
Case Report
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Makiko Sasaki, Takaya Shimura, Hirotada Nishie, Keita Kuroyanagi, Takuya Kanno, Shigeki Fukusada, Naomi Sugimura, Yusuke Mizuno, Takayuki Nukui, Konomu Uno, Yuki Kojima, Ruriko Nishigaki, Mamoru Tanaka, Keiji Ozeki, Eiji Kubota, Hiromi Kataoka, Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Science, Nagoya 467-8601, Japan
Author contributions: Sasaki M contributed to data curation, software, investigation, and writing the original draft; Shimura T contributed to conceptualization, data curation, investigation, and reviewed draft; Nishie H contributed to data curation and investigation; Kuroyanagi K, Kanno T, Fukusada S, Sugimura N, Mizuno Y, Nukui T, Uno K, Kojima Y, Nishigaki R, Tanaka M, Ozeki K, and Kubota E contributed to resources; Kataoka H contributed to supervision; All authors have read and approved the final manuscript.
Informed consent statement: Informed consent has been obtained from the patients’ guardians/next of kin to participate and to publish this paper.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Takaya Shimura, MD, PhD, Associate Professor, Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Science, 1 Kawasumi, Mizuho, Nagoya 467-8601, Japan. tshimura@med.nagoya-cu.ac.jp
Received: April 20, 2024 Revised: May 21, 2024 Accepted: June 3, 2024 Published online: July 15, 2024 Processing time: 82 Days and 23.2 Hours
Abstract
BACKGROUND
BRAF mutation has been recognized as a negative prognostic marker for metastatic colorectal cancer (mCRC), but these data are from common BRAF V600E-mutated mCRC. Combination therapy of BRAF inhibitor and anti-epidermal growth factor receptor (EGFR) antibody has been approved for BRAF V600E-mutated mCRC. However, BRAF non-V600 mutations are rare mutations, and their clinical behavior is not understood. Moreover, the BRAF K601E mutation is extremely rare in mCRC, and there have been no reports on its specific treatment.
CASE SUMMARY
Herein, we report the case of a 59-year-old female with super aggressive mCRC with multiple metastases, which extended to whole body including mediastinal to abdominal lymph nodes, bones, pleura, and peritoneum. The companion diagnostics of tumor tissues showed RAS/BRAF wild-type without microsatellite instability. She received chemotherapy with mFOLFOX6 (oxaliplatin plus infusional 5-fluorouracil [5-FU] and leucovorin) plus panitumumab, following FOLFIRI (irinotecan plus infusional 5-FU and leucovorin) plus ramucirumab. For the next regimen selection, a comprehensive genomic profiling panel was performed and revealed a BRAF K601E mutation, which was not covered in the initial companion diagnostics. After disease progression, a combination of encorafenib, binimetinib, and cetuximab was selected as third-line chemotherapy. The serum levels of tumor markers were immediately decreased accompanied by improvements in pleural effusion and ascites. However, the disease progressed again, and best supportive care was done instead.
CONCLUSION
This case offers novel insights into the clinical behaviors of BRAF non-V600E-mCRC, potentially advancing personalized therapy for rare and aggressive cases.
Core Tip: With the development and standardization of next-generation sequencing, it is anticipated that there will be increased discovery of previously unidentified genetic mutations. BRAF non-V600 mutations including the K601E mutation are rare, and the clinical behavior is not understood. In this case, a comprehensive genomic profiling panel revealed a BRAF K601E mutation, which was not covered in the initial companion diagnostics. A combination of encorafenib, binimetinib, and cetuximab had great effects. It is important to consider the possibility of discovering rare mutations, which could expand treatment options.
