# COMBI-AD

Source: https://onco.cc/trials/combi-ad/  
OnCo record `combi-ad` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-07
- Registry id: NCT01682083
- Phase: 3
- Setting: Resected stage III BRAF V600-mutant melanoma: adjuvant dabrafenib + trametinib 1 year vs placebo
- Sponsor: Novartis
- Enrolled: 870
- Result: 10-year RFS 48% vs 32%; DMFS 63% vs 48%.
- Outcomes: Relapse-free survival at 10 years: Dabrafenib + trametinib 48% vs Placebo 32%; Distant metastasis-free survival at 10 years: Dabrafenib + trametinib 63% vs Placebo 48%
- Replication: No second adjuvant BRAF/MEK phase 3 (BRIM8 with vemurafenib alone was mixed); benefit consistent with metastatic COMBI-d/v data.

## Sources

- ClinicalTrials.gov NCT01682083: https://clinicaltrials.gov/study/NCT01682083
- Final analysis, ASCO 2024: https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.9500

## Connected records

- cancers: [BRAF V600-mutant melanoma](https://onco.cc/cancers/braf-v600-melanoma/), [Melanoma](https://onco.cc/cancers/melanoma/), [Stage III melanoma (after surgery)](https://onco.cc/cancers/stage-iii-melanoma/)
- technologies: [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [BRAF](https://onco.cc/targets/braf/)
- drugs: [Dabrafenib](https://onco.cc/drugs/dabrafenib/), [Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [Trametinib](https://onco.cc/drugs/trametinib/)
- companies: [Novartis](https://onco.cc/companies/novartis/)
- pathways: [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- people: [Georgina V. Long](https://onco.cc/people/georgina-long/)
- key papers: [COMBI-AD: adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma](https://onco.cc/key-papers/paper-combi-ad-nejm-2017/), [Five-Year Analysis of Adjuvant Dabrafenib plus Trametinib in Stage III Melanoma](https://onco.cc/key-papers/paper-combi-ad-n-engl-j-med-2020-update/)
- ideas: [Test intermittent dosing of targeted drugs to delay resistance, with honest priors](https://onco.cc/ideas/idea-tr1-intermittent-dosing-to-delay-resistance/)
- institutions: [Melanoma Institute Australia](https://onco.cc/institutions/melanoma-institute-australia/)
- roadmaps: [Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall](https://onco.cc/roadmaps/targeted-therapy-roadmap/)

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