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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
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.
| Setting | Approach | Guideline |
|---|---|---|
| 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. | not mapped |
| 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. | not mapped |
| Non-V600 BRAF mutations | Treated as driver-negative disease with chemoimmunotherapy; MEK or pan-RAF inhibitor trials. | not mapped |