Reference Detail

Ref Type

Journal Article

PMID

(39072179)

Authors

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

Title

BRAF K601E-mutated metastatic colorectal cancer in response to combination therapy with encorafenib, binimetinib, and cetuximab: A case report.

Journal	Vol	Issue	Date	Pages	Journal Short Title
World journal of gastrointestinal oncology	16	7	2024 Jul 15	3357-3363	World J Gastrointest Oncol

URL

Abstract Text

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.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
BRAF K601E	colon adenocarcinoma	predicted - sensitive	Binimetinib + Cetuximab + Encorafenib	Case Reports/Case Series	Actionable	In a clinical case study, third-line treatment with the combination of Mektovi (binimetinib), Erbitux (cetuximab), and Braftovi (encorafenib) resulted in improvement in the pleural effusion and ascites in a patient with metastatic colon adenocarcinoma harboring BRAF K601E, however, progression occurred after 2 months of treatment (PMID: 39072179).	39072179