BRAF-positive non-small cell lung cancer (NSCLC) treatments can use the BRAF biomarker to provide effective, targeted treatment for this subset of lung cancer.
BRAF-positive NSCLC is an uncommon or rare subtype of lung cancer. The targeted treatments for this subtype of cancer may provide more effective treatment compared to non-specific treatments, such as radiation or chemotherapy.
Targeted treatment means that the medication will only affect cancer cells or those directly related to the cancer. In the case of BRAF, the medications affect the genes responsible for causing defective proteins that lead to the development of BRAF-positive NSCLC.
In order to better understand your treatment options, you need to have a general understanding of BRAF-positive NSCLC and how it affects treatment.
BRAF, short for V-Raf murine sarcoma viral oncogene homolog B1, is both a gene and protein. BRAF proteins, along with another protein called MEK, help to regulate the growth of cells in different organs, such as the lungs.
If you develop a mutation in your BRAF gene, it can cause the creation of abnormal BRAF proteins. This can result in the overgrowth and spread of cells, leading to cancers such as skin or lung cancer.
There are several BRAF mutations, but the one with FDA-approved treatments is BRAF V600E.
BRAF-positive lung cancer accounts for about 3% to 5% of all NSCLC. It is almost exclusively found in the adenocarcinoma subtype of NSCLC. Adenocarcinoma refers to cancer that starts in the outer area of the lungs.
Healthcare professionals can use BRAF as a biomarker, which can help with diagnosis and treatment. However, because of the rarity of BRAF-positive NSCLC, large-scale studies on treatments are minimal.
The treatment options for BRAF-positive NSCLC are relatively limited. The ones that are available provide targeted care. This means that the treatment may be more effective at addressing your cancer if you have a BRAF-positive subtype.
However, like any cancer treatment, several factors affect how you respond to treatment, such as age and overall health. When deciding on your care plan, you will want to review all your possible treatment options and side effects with a doctor.
Dabrafenib plus trametinib
When combined, dabrafenib (Tafinlar) plus trametinib (Mekinist) targets defects in both the BRAF and MEK gene. By fixing the defect in the genes, effective BRAF and MEK proteins help to slow and stop the growth of cancer cells in the lungs.
Studies have shown that the combination of BRAF- and MEK-targeting medications is an effective treatment for people with BRAF-positive NSCLC.
According to a 2023 review, a phase 2 study showed the medication combination achieved an objective response rate (ORR) of about 64%.
Additionally, they found the people who never received treatment had an improved duration of response and longer period of progression-free survival compared to those who had received previous cancer treatment.
In other words, dabrafenib plus trametinib can help to shrink or destroy BRAF-positive NSCLC, provide effectiveness past your last treatment, and increase the length of time you can go without increases in tumor size.
It’s important to note that the trial included less than 200 people, which is on the smaller side. Smaller samples make it harder to make broad generalizations about the effectiveness and safety of the treatment method.
The FDA has approved dabrafenib plus trametinib for use as a first-line treatment for BRAF V600E mutation specifically.
The most commonly reported side effects include:
- diarrhea
- fever
- fatigue
- decreased appetite
- nausea
- hemorrhage
- vomiting
- swelling
- cough
- dry skin
- rash
- chills
- dyspnea or shortness of breath
Encorafenib and binimetinib
Encorafenib (Braftovi) and binimetinib (Mektovi) gained FDA approval in
Clinical trials showed that the ORR was 75% in people who had not had previous treatment. People in the study who had had previous treatment showed an ORR of 46%.
The clinical study the FDA cited had fewer than 100 people involved.
About a quarter of people involved in the study experienced side effects. The most common included:
- fatigue
- nausea
- cough
- diarrhea
- musculoskeletal pain
- vomiting
- shortness of breath
- abdominal pain
- rash
- visual impairment
- constipation
Immunotherapy with or without chemotherapy
If targeted treatments do not work, your treatment team may consider immunotherapy with or without chemotherapy.
Immunotherapy is a type of treatment that trains your own immune system to target the cancer cells in your lungs or other areas of your body.
Chemotherapy is a common type of systemic cancer treatment that uses different medications to help shrink and destroy tumors. Because it is systemic, chemotherapy can cause damage to healthy cells, leading to potentially bad side effects.
Immunotherapy with or without chemotherapy is the standard first-line treatment if you have a different BRAF mutation than V600E.
Clinical trials
Clinical trials allow pharmaceutical companies to test the effectiveness and safety of new or novel targeted treatment options.
If you are interested in joining a clinical study, you can talk with your doctor about any potential options in your area.
You can also search for clinical trials using Clinicaltrials.gov.
Not everyone qualifies to participate in a trial. Your doctor will be able to provide better answers about whether you may qualify.
Clinical trials can help advance new treatments, but they are not without risk. Make sure to discuss the possible risks of joining a trial with a doctor before signing up.
Targeted treatments for BRAF-positive NSCLC consist of two different drug combinations that target the BRAF and MEK genes to help stop the growth of cancer. Evidence suggests both combinations provide safe and effective treatment for the V600E BRAF mutation.
If you do not have V600E variation, the standard of treatment includes immunotherapy with or without chemotherapy.