# BRAF V600E-mutant non-small-cell lung cancer

Source: https://onco.cc/cancers/braf-v600e-nsclc/  
OnCo record `braf-v600e-nsclc` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: BRAF-mutant lung cancer; BRAF V600E NSCLC; BRAF V600-mutated lung adenocarcinoma
- Tags: subtype-page; lung
- Group: lung
- Burden: 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.
- Subtypes: BRAF V600E adenocarcinoma, treatment-naive (BRAF plus MEK inhibitor or chemoimmunotherapy); BRAF V600E adenocarcinoma after chemotherapy or immunotherapy; Non-V600 BRAF mutations, class II and III (not sensitive to BRAF inhibitors)
- Biomarkers: BRAF V600E by sequencing (immunohistochemistry as a screen); BRAF mutation class (V600 versus non-V600); PD-L1 tumour proportion score (immunotherapy is active in BRAF-mutant disease); Left ventricular function, eye examination and temperature on BRAF plus MEK inhibitors

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/braf-v600e-nsclc/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/braf-v600e-nsclc/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/braf-v600e-nsclc/#what-it-is [3 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/braf-v600e-nsclc/#finding-it [4 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/braf-v600e-nsclc/#treating-it [3 settings, 3 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/braf-v600e-nsclc/#evidence [3 trials, 3 key papers, 3 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/braf-v600e-nsclc/#science [5 targets, 2 pathways]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/braf-v600e-nsclc/where-you-are/ [34 UK centres]
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/braf-v600e-nsclc/#living-with-it [16 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/braf-v600e-nsclc/coming/ [8 medicines, 3 trials, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/braf-v600e-nsclc/data/ [37 connected records]

## Standard of care

- Advanced BRAF V600E, first line: Dabrafenib plus trametinib or encorafenib plus binimetinib (PHAROS); pembrolizumab with platinum doublet is an alternative, particularly with high PD-L1. ([Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [Dabrafenib](https://onco.cc/drugs/dabrafenib/), [Trametinib](https://onco.cc/drugs/trametinib/), [Encorafenib](https://onco.cc/drugs/encorafenib/), [Binimetinib](https://onco.cc/drugs/binimetinib/), [PHAROS](https://onco.cc/trials/pharos/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [BRAF V600E mutation](https://onco.cc/terms/braf-v600-mutation/))
- Advanced BRAF V600E, after targeted therapy: Pembrolizumab plus platinum doublet, or the other BRAF plus MEK pair if the first was stopped for toxicity rather than progression. ([Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Pemetrexed](https://onco.cc/drugs/pemetrexed/), [Encorafenib](https://onco.cc/drugs/encorafenib/), [Binimetinib](https://onco.cc/drugs/binimetinib/))
- Non-V600 BRAF mutations: Treated as driver-negative disease with chemoimmunotherapy; MEK or pan-RAF inhibitor trials. ([Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Pemetrexed](https://onco.cc/drugs/pemetrexed/), [Trametinib](https://onco.cc/drugs/trametinib/))

## State of the art

- Two approved BRAF plus MEK inhibitor pairs with response rates of 64 to 75 percent in untreated disease.
- Immunotherapy is active, giving a genuine choice of sequence unlike most driver subtypes.
- Non-V600 mutations remain without a targeted drug.

## Open problems

- No randomised trial compares BRAF plus MEK inhibitors with chemoimmunotherapy first line or settles the sequence.
- Non-V600 BRAF mutations, half of cases, have no approved targeted therapy.
- Resistance through MAPK reactivation has no established next step.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/BRAF_(gene)
- Wikipedia: https://en.wikipedia.org/wiki/BRAF_(gene)
- NCCN Guidelines: Non-Small Cell Lung Cancer: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1450

## Connected records

- cancers: [EGFR-mutated non-small-cell lung cancer](https://onco.cc/cancers/egfr-mutant-nsclc/), [HER2-mutant non-small-cell lung cancer](https://onco.cc/cancers/her2-mutant-nsclc/), [KRAS G12C-mutant non-small-cell lung cancer](https://onco.cc/cancers/kras-g12c-nsclc/), [MET exon 14 and MET-amplified non-small-cell lung cancer](https://onco.cc/cancers/met-altered-nsclc/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [NTRK fusion-positive non-small-cell lung cancer](https://onco.cc/cancers/ntrk-fusion-nsclc/), [PD-L1-high non-small-cell lung cancer without a driver mutation](https://onco.cc/cancers/pdl1-high-nsclc/), [RET fusion-positive non-small-cell lung cancer](https://onco.cc/cancers/ret-fusion-nsclc/), [ROS1-positive non-small-cell lung cancer](https://onco.cc/cancers/ros1-positive-nsclc/)
- technologies: [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [BRAF](https://onco.cc/targets/braf/), [PD-1](https://onco.cc/targets/pd1/), [PD-L1](https://onco.cc/targets/pdl1/)
- drugs: [Binimetinib](https://onco.cc/drugs/binimetinib/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Dabrafenib](https://onco.cc/drugs/dabrafenib/), [Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [Encorafenib](https://onco.cc/drugs/encorafenib/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Pemetrexed](https://onco.cc/drugs/pemetrexed/), [Trametinib](https://onco.cc/drugs/trametinib/)
- companies: [Novartis](https://onco.cc/companies/novartis/), [Pfizer (incl. Seagen)](https://onco.cc/companies/pfizer/)
- pathways: [Non-small cell lung cancer (KEGG map)](https://onco.cc/pathways/nsclc-signalling/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- terms: [BRAF V600E mutation](https://onco.cc/terms/braf-v600-mutation/), [Driver mutation](https://onco.cc/terms/driver-mutation/), [Drug resistance (primary and acquired)](https://onco.cc/terms/resistance/), [Tumour proportion score (TPS)](https://onco.cc/terms/tps/)
- trials: [BRF113928 cohort C (dabrafenib with trametinib, untreated BRAF V600E)](https://onco.cc/trials/brf113928/), [PHAROS](https://onco.cc/trials/pharos/), [Phase II Study Investigating the Combination of Encorafenib and Binimetinib in BRAF V600E Mutated Chinese Patients With Metastatic Non-Small Cell Lung](https://onco.cc/trials/nct05195632/)
- people: [David Planchard](https://onco.cc/people/david-planchard/), [Gregory J. Riely](https://onco.cc/people/gregory-riely/)
- key papers: [Dabrafenib plus trametinib in previously treated BRAF V600E-mutant metastatic non-small-cell lung cancer](https://onco.cc/key-papers/paper-planchard-dabrafenib-trametinib-braf-nsclc-lancet-oncol-2016/), [Dabrafenib plus trametinib in previously untreated BRAF V600E-mutant metastatic non-small-cell lung cancer](https://onco.cc/key-papers/paper-planchard-dabrafenib-trametinib-first-line-lancet-oncol-2017/), [PHAROS: encorafenib plus binimetinib in BRAF V600E-mutant metastatic non-small-cell lung cancer](https://onco.cc/key-papers/paper-pharos-encorafenib-binimetinib-riely-jco-2023/)

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JSON: https://onco.cc/api/v1/entities/braf-v600e-nsclc.json