Published online Jul 15, 2024. doi: 10.4251/wjgo.v16.i7.3357
Revised: May 21, 2024
Accepted: June 3, 2024
Published online: July 15, 2024
Processing time: 82 Days and 23.2 Hours
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.
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.
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.