{"entity":{"id":"combi-ad","kind":"trial","name":"COMBI-AD","aka":[],"tldr":"A year of two targeted pills after surgery halves the risk of relapse in BRAF-mutant melanoma, and the benefit is still visible a decade later.","summary":"RFS HR 0.47 at first analysis; final analysis (JCO 2024, >10 years) reported 10-year RFS 48% vs 32% and DMFS 63% vs 48%. OS analysis was hampered by crossover and subsequent immunotherapy. The longest follow-up of any adjuvant melanoma trial; the alternative to adjuvant PD-1 for BRAF-mutant patients.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT01682083","url":"https://clinicaltrials.gov/study/NCT01682083"},{"label":"Final analysis, ASCO 2024","url":"https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.9500"}],"tags":[],"related":[],"cancers":["melanoma","braf-v600-melanoma","stage-iii-melanoma"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["braf"],"drugs":["dabrafenib-trametinib"],"companies":["novartis"],"institutions":[],"pathways":["ras-mapk"],"terms":[],"trials":[],"people":["georgina-long"],"bottlenecks":[],"keyPapers":["paper-combi-ad-nejm-2017","paper-combi-ad-n-engl-j-med-2020-update"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT01682083","phase":"3","setting":"Resected stage III BRAF V600-mutant melanoma: adjuvant dabrafenib + trametinib 1 year vs placebo","sponsor":"Novartis","result":"10-year RFS 48% vs 32%; DMFS 63% vs 48%.","started":"2013-01-08","startedType":"actual","yearReported":2017,"enrolled":870,"enrolledBasis":"registry","outcomes":[{"endpoint":"Relapse-free survival at 10 years","primary":true,"unit":"%","arms":[{"name":"Dabrafenib + trametinib","value":48},{"name":"Placebo","value":32}],"source":"https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.9500"},{"endpoint":"Distant metastasis-free survival at 10 years","unit":"%","arms":[{"name":"Dabrafenib + trametinib","value":63},{"name":"Placebo","value":48}],"source":"https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.9500"}],"replication":"No second adjuvant BRAF/MEK phase 3 (BRIM8 with vemurafenib alone was mixed); benefit consistent with metastatic COMBI-d/v data."},"route":"/trials/combi-ad/","neighbours":{"cancer":[{"id":"braf-v600-melanoma","kind":"cancer","name":"BRAF V600-mutant melanoma","route":"/cancers/braf-v600-melanoma/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"stage-iii-melanoma","kind":"cancer","name":"Stage III melanoma (after surgery)","route":"/cancers/stage-iii-melanoma/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"}],"drug":[{"id":"dabrafenib","kind":"drug","name":"Dabrafenib","route":"/drugs/dabrafenib/"},{"id":"dabrafenib-trametinib","kind":"drug","name":"Dabrafenib + trametinib","route":"/drugs/dabrafenib-trametinib/"},{"id":"trametinib","kind":"drug","name":"Trametinib","route":"/drugs/trametinib/"}],"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/"}],"person":[{"id":"georgina-long","kind":"person","name":"Georgina V. Long","route":"/people/georgina-long/"}],"paper":[{"id":"paper-combi-ad-nejm-2017","kind":"paper","name":"COMBI-AD: adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma","route":"/key-papers/paper-combi-ad-nejm-2017/"},{"id":"paper-combi-ad-n-engl-j-med-2020-update","kind":"paper","name":"Five-Year Analysis of Adjuvant Dabrafenib plus Trametinib in Stage III Melanoma","route":"/key-papers/paper-combi-ad-n-engl-j-med-2020-update/"}],"idea":[{"id":"idea-tr1-intermittent-dosing-to-delay-resistance","kind":"idea","name":"Test intermittent dosing of targeted drugs to delay resistance, with honest priors","route":"/ideas/idea-tr1-intermittent-dosing-to-delay-resistance/"}],"institution":[{"id":"melanoma-institute-australia","kind":"institution","name":"Melanoma Institute Australia","route":"/institutions/melanoma-institute-australia/"}],"roadmap":[{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"}]}}