Cancer is a complex disease in which genetic changes can influence how cancer cells grow, divide, and survive. However, it is not always driven by the same changes in every patient. Advances in diagnostics and molecular profiling have therefore transformed the way cancer is understood and managed. Treatment is increasingly moving beyond simply asking, "Where is the cancer?" to also asking, "What molecular changes are driving its growth?" For example, colorectal cancers and melanomas harbour a range of genetic mutations that influence tumour behaviour and treatment options. One such common genetic alteration is the BRAF V600E mutation, a specific change in the BRAF gene that can lead to abnormal cell growth and proliferation. Identifying these underlying genetic alterations can help clinicians better understand the biology of a tumour and, in selected cancers, guide the use of targeted treatment approaches.
What is BRAF gene and BRAF V600E mutation?
The BRAF gene plays a key role in controlling how cells grow and divide. When a spontaneous change or mutation occurs in this gene, it can cause the gene to malfunction. This malfunction results in uncontrolled cell growth. Among the many possible BRAF mutations, V600E is by far the most common. In colorectal cancer (CRC), it accounts for roughly 80% of all reported BRAF mutations. [1] In melanoma, activating BRAF mutations are found in approximately 50% of cases, and more than 90% of these are the V600E variant. [2] In non-small cell lung cancer (NSCLC), BRAF V600E accounts for an estimated 1–2% of cases, a small but clinically actionable subset. Because of how central this mutation is to tumor behavior, detecting it carries real clinical value, both as a prognostic marker and as a guide to treatment, since it identifies patients who may benefit from targeted BRAF inhibitors such as Braftovi. [3,4]
What is Braftovi?
BRAFTOVI is the brand name for encorafenib, a targeted therapy designed for cancers driven by a BRAF V600 mutation. It works by blocking the abnormal BRAF protein, which in turn prevents the protein from triggering uncontrolled cell division, slowing the growth and spread of the cancer.
Braftovi is used in combination with another medicine, binimetinib, to treat:
- melanoma (a skin cancer) that cannot be removed by surgery or has spread;
- a type of lung cancer called non-small cell lung cancer (NSCLC). It is used when the cancer is advanced and has the BRAF V600E mutation;
Braftovi is also used to treat colorectal cancer (cancer of the large bowel or rectum) when the cancer has the BRAF V600E mutation and is metastatic (has spread elsewhere in the body):
- in combination with cetuximab and FOLFOX (a combination of fluorouracil with folinic acid and the cancer medicine oxaliplatin)) in previously untreated patients;
- in combination with cetuximab in patients who have already been treated with cancer medicines given by mouth or by injection.
Why is the detection of BRAF V600E mutation important?
Clinical research has consistently linked BRAF mutations to poorer outcomes in metastatic CRC. Randomized trials suggest that patients with BRAF-mutant metastatic CRC tend to be more resistant to standard chemotherapy, and roughly 10-20% of them also have microsatellite instability (MSI), a factor that can further influence treatment response and overall prognosis. [1,7] Patients with BRAF V600E-mutated CRC generally face a significantly worse prognosis and lower quality of life, often experiencing faster disease progression and shorter life expectancy. [8]
The same mutation plays an outsized role in melanoma, where BRAF V600E is the most common genetic alteration. Identifying it early is essential for effective disease management, enabling targeted therapy that can improve overall survival. [9] Multiple studies have tied BRAF mutations to unfavourable prognosis, including reduced survival in stage IV melanoma, and BRAF V600E-mutated melanomas are often described as behaving more aggressively. [10]
Studies have also shown that patients with BRAF V600E-mutated advanced NSCLC tend to have poor outcomes on standard chemotherapy and appear relatively insensitive to platinum-based regimens. [11]
The clinical stakes of identifying this mutation were underscored by the pivotal BREAKWATER trial in colorectal cancer, where adding Braftovi and cetuximab to chemotherapy nearly doubled median overall survival compared with chemotherapy alone, 30.3 months versus 15.1 months. Results like these illustrate how much outcomes can shift once the right molecular target is confirmed and treated accordingly. [12]
Because of this, testing for BRAF V600E and other genomic biomarkers is a routine, guideline-recommended part of the diagnostic workup for metastatic CRC in Canada, helping guide appropriate therapy selection. [8]
What Does a BRAF V600E Mutation measure?
A BRAF V600E test analyzes tumor DNA extracted from preserved tissue to check whether the V600E variant of the BRAF gene is present. Key features of the test include:
- Mutation detection: The test uses Real Time PCR, a technique that amplifies and analyses DNA, to identify whether the V600E mutation is present or absent in the tumour sample.
- Qualitative result: The result is reported simply as "Detected" or "Not Detected."
What happens during a BRAF genetic test?
For solid tumors, testing typically uses a sample of tumor cells, which may be obtained:
- During surgery, if the entire tumor is being removed.
- Via biopsy, if only a small tissue sample is needed. The specific type of biopsy depends on the tumor's location and may involve:
- A hollow needle inserted through the skin, sometimes guided by imaging such as ultrasound.
- A minor surgical procedure to remove a tissue sample (an incisional biopsy).
Are there any risks to the test?
The risks depend largely on how the sample is collected. With a biopsy, some soreness, pain, or bleeding at the site is possible. It's worth discussing your specific risks with your healthcare provider.
What is the most important information I should know about BRAFTOVI?
BRAFTOVI can cause serious side effects, including an increased risk of new skin cancers, specifically cutaneous squamous cell carcinoma or basal cell carcinoma.
Talk to your healthcare provider about your individual risk, and check your skin regularly. Report any of the following right away:
- A new wart
- A skin sore or reddish bump that bleeds or doesn't heal
- A change in the size or color of a mole
Questions to Ask Before Starting Braftovi?
Starting a new cancer treatment can feel overwhelming. These questions can help guide the conversation with your care team:
- Has my tumor been tested for the BRAF V600E mutation, and which test was used?
- Is Braftovi appropriate for my specific cancer type and stage?
- Which other medicines will Braftovi be combined with, and why?
- What side effects should I watch for and report right away?
- How often will my heart, liver, and skin be checked during treatment?
Medical Disclaimer:
This information is provided for educational purposes only and is not a substitute for professional medical advice. Medicine should only be taken under the guidance of a qualified healthcare provider. Patients should always consult their doctor for advice on diagnosis, treatment, and medication use, and should not make changes to their prescribed therapy without medical supervision.
References:
- Roma, C., Rachiglio, A. M., Pasquale, R., Fenizia, F., Iannaccone, A., Tatangelo, F., … Normanno, N. (2016). BRAF V600E mutation in metastatic colorectal cancer: Methods of detection and correlation with clinical and pathologic features. Cancer Biology & Therapy, 17(8), 840–848.
- Ascierto, P.A., Kirkwood, J.M., Grob, JJ. et al.The role of BRAF V600 mutation in melanoma. J Transl Med 10, 85 (2012). https://doi.org/10.1186/1479-5876-10-85
- Lasota J, Kowalik A, Wasag B, Wang ZF, Felisiak-Golabek A, Coates T, Kopczynski J, Gozdz S, Miettinen M. Detection of the BRAF V600E mutation in colon carcinoma: critical evaluation of the imunohistochemical approach. Am J Surg Pathol. 2014 Sep;38(9):1235-41
- Planchard D, Sanborn RE, Negrao MV, Vaishnavi A, Smit EF. BRAFV600E-mutant metastatic NSCLC: disease overview and treatment landscape. NPJ Precis Oncol. 2024 Apr 16;8(1):90. doi: 10.1038/s41698-024-00552-7. Erratum in: NPJ Precis Oncol. 2024 Jul 15;8(1):142.
- European Medicines Agency (EMA). Braftovi (encorafenib): European Public Assessment Report (EPAR). Amsterdam: European Medicines Agency. EMA – Braftovi EPAR
- Health Canada. BRAFTOVI (encorafenib) Product Monograph. Pfizer Canada ULC; revised March 30, 2021
- Roma C, Rachiglio AM, Pasquale R, Fenizia F, Iannaccone A, Tatangelo F, Antinolfi G, Parrella P, Graziano P, Sabatino L, Colantuoni V, Botti G, Maiello E, Normanno N. BRAF V600E mutation in metastatic colorectal cancer: Methods of detection and correlation with clinical and pathologic features. Cancer Biol Ther. 2016 Aug 2;17(8):840-8
- Encorafenib (Braftovi): Therapeutic area: Metastatic colorectal cancer with a BRAF V600E mutation: Reimbursement Review [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2026 Apr
- Finke, C., Mohr, P. BRAFV600E Metastatic Melanoma Journey: A Perspective from a Patient and his Oncologist. Adv Ther 41, 2576–2585 (2024)
- Avădănei, E.-R.; Căruntu, I.-D.; Nucă, I.; Balan, R.; Lozneanu, L.; Giusca, S.-E.; Amalinei, C. BRAF V600E Mutation in Malignant Melanoma—A Romanian Research Experience. Medicina2024, 60, 351
- Yan N, Guo S, Zhang H, Zhang Z, Shen S, Li X. BRAF-Mutated Non-Small Cell Lung Cancer: Current Treatment Status and Future Perspective. Front Oncol. 2022 Mar 31;12:863043
- Elez E, Yoshino T, Shen L, Lonardi S, Van Cutsem E, Eng C, Kim TW, Wasan HS, Desai J, Ciardiello F, Yaeger R, Maughan TS, Morris VK, Wu C, Usari T, Laliberte R, Dychter SS, Zhang X, Tabernero J, Kopetz S; BREAKWATER Trial Investigators. Encorafenib, Cetuximab, and mFOLFOX6 in BRAF-Mutated Colorectal Cancer. N Engl J Med. 2025 Jun 26;392(24):2425-2437
- Lupin Diagnostics. BRAF V600E Mutation, FFPE Tissue Test. Lupin Diagnostics.
- BRAF Genetic Test. U.S. National Library of Medicine, National Institutes of Health
