{"entity":{"id":"dabrafenib-trametinib","kind":"drug","name":"Dabrafenib + trametinib","aka":[],"tldr":"Dabrafenib plus trametinib is the BRAF-plus-MEK pill combination, approved for BRAF V600E lung cancer and, since 2022, for any solid tumour with that mutation.","summary":"Dabrafenib blocks BRAF V600 and trametinib is an allosteric MEK1/2 inhibitor; blocking two consecutive steps of the MAPK pathway (vertical blockade) prevents the paradoxical reactivation seen with BRAF inhibitors alone. In BRAF V600E non-small-cell lung cancer (about 2% of adenocarcinomas) the combination gave an ORR of 64% first line with median PFS of about 10.8 months (BRF113928), and it is an established doublet in BRAF-mutant melanoma and thyroid cancer. A tumour-agnostic approval followed in June 2022 for BRAF V600E solid tumours (excluding colorectal) in patients aged 6 and over. Pyrexia is the characteristic toxicity and the usual reason for dose interruptions. Encorafenib plus binimetinib (PHAROS, 2023) is the alternative doublet in lung cancer. In short, if a tumour carries BRAF V600E, this pair of pills is a treatment option in most tissue types.","status":"approved","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Dabrafenib","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Dabrafenib"},{"label":"NICE TA898: dabrafenib plus trametinib for BRAF V600 mutation-positive advanced non-small-cell lung cancer","url":"https://www.nice.org.uk/guidance/ta898"}],"tags":[],"related":["braf-plus-mek","braf-v600e"],"cancers":["nsclc","melanoma","thyroid","paediatric-low-grade-glioma","paediatric-high-grade-glioma","secondary-brain-tumours","braf-v600e-nsclc","braf-v600-melanoma","stage-iii-melanoma","advanced-melanoma","lung-cancer"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["braf"],"drugs":[],"companies":["novartis"],"institutions":[],"pathways":["ras-mapk"],"terms":["tumour-agnostic"],"trials":["brf113928","pharos"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Tafinlar + Mekinist","modality":"Small-molecule kinase inhibitors (BRAF + MEK)","mechanism":"BRAF V600 inhibitor plus allosteric MEK1/2 inhibitor; vertical blockade prevents paradoxical MAPK reactivation.","approvals":[{"region":"US","year":2014,"indication":"BRAF V600E/K unresectable or metastatic melanoma, combination (accelerated; each drug alone approved 2013)"},{"region":"US","year":2017,"indication":"BRAF V600E metastatic NSCLC"},{"region":"US","year":2022,"indication":"BRAF V600E solid tumours, tumour-agnostic (age ≥6)"},{"region":"England (NICE)","year":2023,"indication":"BRAF V600 mutation-positive advanced non-small-cell lung cancer, first line only","note":"TA898, published 14 June 2023, recommends the combination only as first-line treatment of advanced disease, subject to the commercial arrangement. A patient who has already had chemotherapy or immunotherapy is not funded for it."}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[]},"route":"/drugs/dabrafenib-trametinib/","neighbours":{"pairing":[{"id":"braf-plus-mek","kind":"pairing","name":"BRAF inhibitor + MEK inhibitor","route":"/pairings/braf-plus-mek/"},{"id":"braf-mek-neoadjuvant-atc","kind":"pairing","name":"BRAF/MEK inhibition → surgery in anaplastic thyroid cancer","route":"/pairings/braf-mek-neoadjuvant-atc/"},{"id":"io-first-then-braf-mek","kind":"pairing","name":"Immunotherapy first, then BRAF/MEK (BRAF-mutant melanoma)","route":"/pairings/io-first-then-braf-mek/"},{"id":"redifferentiation-rai","kind":"pairing","name":"MAPK inhibitor redifferentiation → radioiodine","route":"/pairings/redifferentiation-rai/"}],"biomarker":[{"id":"braf-v600e","kind":"biomarker","name":"BRAF V600E (and V600K)","route":"/biomarkers/braf-v600e/"}],"cancer":[{"id":"acral-melanoma","kind":"cancer","name":"Acral melanoma","route":"/cancers/acral-melanoma/"},{"id":"advanced-melanoma","kind":"cancer","name":"Advanced melanoma (unresectable stage III and stage IV)","route":"/cancers/advanced-melanoma/"},{"id":"ampullary","kind":"cancer","name":"Ampullary cancer (ampulla of Vater)","route":"/cancers/ampullary/"},{"id":"cholangiocarcinoma","kind":"cancer","name":"Biliary tract cancer (cholangiocarcinoma)","route":"/cancers/cholangiocarcinoma/"},{"id":"braf-v600-melanoma","kind":"cancer","name":"BRAF V600-mutant melanoma","route":"/cancers/braf-v600-melanoma/"},{"id":"braf-v600e-nsclc","kind":"cancer","name":"BRAF V600E-mutant non-small-cell lung cancer","route":"/cancers/braf-v600e-nsclc/"},{"id":"secondary-brain-tumours","kind":"cancer","name":"Brain metastases (secondary brain tumours)","route":"/cancers/secondary-brain-tumours/"},{"id":"craniopharyngioma","kind":"cancer","name":"Craniopharyngioma","route":"/cancers/craniopharyngioma/"},{"id":"erdheim-chester-disease","kind":"cancer","name":"Erdheim-Chester disease","route":"/cancers/erdheim-chester-disease/"},{"id":"histiocytoses","kind":"cancer","name":"Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms","route":"/cancers/histiocytoses/"},{"id":"extrahepatic-cholangiocarcinoma","kind":"cancer","name":"Extrahepatic cholangiocarcinoma (perihilar and distal)","route":"/cancers/extrahepatic-cholangiocarcinoma/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"},{"id":"hairy-cell-leukemia","kind":"cancer","name":"Hairy cell leukaemia","route":"/cancers/hairy-cell-leukemia/"},{"id":"kras-wild-type-pdac","kind":"cancer","name":"KRAS wild-type pancreatic ductal adenocarcinoma","route":"/cancers/kras-wild-type-pdac/"},{"id":"langerhans-cell-histiocytosis","kind":"cancer","name":"Langerhans cell histiocytosis (LCH)","route":"/cancers/langerhans-cell-histiocytosis/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"metastatic-pdac","kind":"cancer","name":"Metastatic pancreatic ductal adenocarcinoma","route":"/cancers/metastatic-pdac/"},{"id":"lch-multisystem","kind":"cancer","name":"Multisystem Langerhans cell histiocytosis (with or without risk-organ involvement)","route":"/cancers/lch-multisystem/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"paediatric-high-grade-glioma","kind":"cancer","name":"Paediatric high-grade glioma (excluding diffuse midline 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inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"}],"company":[{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"}],"pathway":[{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"term":[{"id":"lung-uk-drug-access","kind":"term","name":"Lung cancer drugs in England: what NICE has recommended","route":"/terms/lung-uk-drug-access/"},{"id":"race-for-children-act","kind":"term","name":"RACE for Children Act","route":"/terms/race-for-children-act/"},{"id":"tumour-agnostic","kind":"term","name":"Tumour-agnostic (tissue-agnostic) approval","route":"/terms/tumour-agnostic/"}],"trial":[{"id":"brf113928","kind":"trial","name":"BRF113928 cohort C (dabrafenib with trametinib, untreated BRAF V600E)","route":"/trials/brf113928/"},{"id":"combi-ad","kind":"trial","name":"COMBI-AD","route":"/trials/combi-ad/"},{"id":"combi-d","kind":"trial","name":"COMBI-d","route":"/trials/combi-d/"},{"id":"dreamseq","kind":"trial","name":"DREAMseq (ECOG-ACRIN EA6134)","route":"/trials/dreamseq/"},{"id":"pharos","kind":"trial","name":"PHAROS","route":"/trials/pharos/"},{"id":"roar-atc","kind":"trial","name":"ROAR (anaplastic thyroid cancer cohort)","route":"/trials/roar-atc/"},{"id":"roar","kind":"trial","name":"ROAR (Rare Oncology Agnostic Research) basket: BRAF V600E biliary tract cancer cohort","route":"/trials/roar/"},{"id":"tadpole","kind":"trial","name":"TADPOLE (CDRB436G2201)","route":"/trials/tadpole/"}],"idea":[{"id":"idea-atc-triplet-io","kind":"idea","name":"BRAF/MEK plus PD-1 blockade as standard for BRAF-mutant anaplastic thyroid cancer","route":"/ideas/idea-atc-triplet-io/"}],"person":[{"id":"keith-flaherty","kind":"person","name":"Keith T. Flaherty","route":"/people/keith-flaherty/"}],"drug":[{"id":"dabrafenib","kind":"drug","name":"Dabrafenib","route":"/drugs/dabrafenib/"},{"id":"trametinib","kind":"drug","name":"Trametinib","route":"/drugs/trametinib/"}],"roadmap":[{"id":"paediatric-oncology-roadmap","kind":"roadmap","name":"Paediatric oncology roadmap: cooperative-group cures → engineered immunity → drugs developed for children first","route":"/roadmaps/paediatric-oncology-roadmap/"},{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"}]}}