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BRAF V600E lung cancer carries the same mutation as many melanomas and is treated with the same pairs of pills that block BRAF and MEK together. Dabrafenib with trametinib and encorafenib with binimetinib each shrink about two thirds to three quarters of untreated tumours.
BRAF V600E lung cancer was recognised as a targetable subtype after the melanoma experience, in which BRAF inhibitors alone produced responses that were quickly lost through MEK reactivation and paradoxical pathway activation, so combined BRAF and MEK blockade became the rule. In the phase 2 BRF113928 study dabrafenib plus trametinib produced response rates of 64 percent in treatment-naive and 63 percent in previously treated patients with median progression-free survival of about 10 months, and the FDA approved the combination for BRAF V600E lung cancer in June 2017, the first targeted therapy for this driver.
PHAROS (2023) tested encorafenib plus binimetinib in the same population: response rates of 75 percent in 59 treatment-naive and 46 percent in 39 previously treated patients, with fewer of the fevers that interrupt dabrafenib and trametinib, and the combination was approved in October 2023. Both pairs are given until progression; pyrexia, fatigue, nausea, rash and cardiac and eye toxicity are monitored. BRAF V600E lung cancers often express PD-L1 and, unlike EGFR or ALK disease, respond to checkpoint inhibitors, so chemoimmunotherapy is a reasonable alternative first line and the standard afterwards.
Non-V600 BRAF mutations (class II and III), the other half of BRAF-mutant lung cancers, do not respond to BRAF plus MEK inhibitors and are treated as driver-negative disease; MEK inhibitors and pan-RAF inhibitors are in trials for them. Open questions are the sequence of targeted therapy and immunotherapy and how to treat resistance, which usually arises through reactivation of the MAPK pathway.
BRAF mutations occur in 2 to 4 percent of non-small-cell lung cancers, about half of them V600E; unlike most drivers they are found in current or former smokers as often as in never-smokers.
Central tumours arise in the large airways, peripheral ones in the alveoli; both drain to hilar then mediastinal nodes, and the pleural lining is a separate cancer site.
Same organ: Mediastinal germ cell tumour, Pleuropulmonary blastoma (types I, Ir, II and III), Type A and type AB thymoma, Type B1 and type B2 thymoma, Type B3 thymoma, Micronodular thymoma with lymphoid stroma, Adenocarcinoma of the lung, Squamous cell carcinoma of the lung, Large cell carcinoma of the lung, Sarcomatoid carcinoma of the lung, Adenosquamous carcinoma of the lung, Invasive mucinous adenocarcinoma of the lung, Adenocarcinoma in situ and minimally invasive adenocarcinoma of the lung, Basaloid squamous cell carcinoma of the lung, Lymphoepithelial carcinoma of the lung, Pulmonary blastoma (adult), Non-small-cell lung cancer, Lung cancer (all types), Small-cell lung cancer, Mesothelioma, Pleural mesothelioma, Thymoma and thymic carcinoma, Childhood lung and airway tumours (pleuropulmonary blastoma, tracheobronchial tumours), Inflammatory myofibroblastic tumour (IMT), EGFR-mutated non-small-cell lung cancer, ALK-positive non-small-cell lung cancer, KRAS G12C-mutant non-small-cell lung cancer, ROS1-positive non-small-cell lung cancer, MET exon 14 and MET-amplified non-small-cell lung cancer, RET fusion-positive non-small-cell lung cancer, HER2-mutant non-small-cell lung cancer, NTRK fusion-positive non-small-cell lung cancer, PD-L1-high non-small-cell lung cancer without a driver mutation, Resectable stage I to III non-small-cell lung cancer, Unresectable stage III non-small-cell lung cancer, Limited-stage small-cell lung cancer, Extensive-stage small-cell lung cancer, Lung neuroendocrine tumours (typical and atypical carcinoid), Large cell neuroendocrine carcinoma of the lung, Thymoma (WHO types A, AB, B1, B2 and B3), Thymic carcinoma
Dabrafenib plus trametinib or encorafenib plus binimetinib (PHAROS); pembrolizumab with platinum doublet is an alternative, particularly with high PD-L1.
Pembrolizumab plus platinum doublet, or the other BRAF plus MEK pair if the first was stopped for toxicity rather than progression.
Treated as driver-negative disease with chemoimmunotherapy; MEK or pan-RAF inhibitor trials.
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Encorafenib-binimetinib is approved for BRAF V600E lung cancer and offers a second targeted option, particularly for patients troubled by fever on dabrafenib-trametinib.
BRAF plus MEK inhibition is a standard first-line option for BRAF V600E lung cancer, with chemo-immunotherapy as the alternative or subsequent line.
BRAF V600E is a routinely tested lung cancer driver, and BRAF plus MEK inhibition is the standard targeted therapy for it.
Query for this cancer: (TITLE:"BRAF V600E-mutant non-small-cell lung cancer" OR ABSTRACT:"BRAF V600E-mutant non-small-cell lung cancer" OR TITLE:"BRAF-mutant lung cancer" OR ABSTRACT:"BRAF-mutant lung cancer" OR TITLE:"BRAF V600E NSCLC" OR ABSTRACT:"BRAF V600E NSCLC" OR TITLE:"BRAF V600-mutated lung adenocarcinoma" OR ABSTRACT:"BRAF V600-mutated lung adenocarcinoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about BRAF V600E-mutant non-small-cell lung cancer, not a curated reading list.
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Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
Dabrafenib: take on an empty stomach. Trametinib: take on an empty stomach; both cause pyrexia.
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
See all on the product pages:BinimetinibCarboplatinDabrafenibDabrafenib + trametinibEncorafenibPembrolizumabPemetrexedTrametinib·Printable cards in the navigator
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