# Immunotherapy first, then BRAF/MEK (BRAF-mutant melanoma)

Source: https://onco.cc/pairings/io-first-then-braf-mek/  
OnCo record `io-first-then-braf-mek` (Pairing). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

In BRAF-mutant melanoma, start with immunotherapy and keep the targeted pills in reserve; the reverse order costs lives.

## Summary

This sequence rule for BRAF-mutant melanoma is to start with immune checkpoint inhibitors, nivolumab with ipilimumab, and to keep the BRAF/MEK inhibitors dabrafenib and trametinib, or encorafenib-based therapy, in reserve. Immunotherapy responses are durable and can be curative, whereas BRAF/MEK responses are fast but nearly always temporary, so using the durable option first preserves the fast option as a rescue. The phase 3 DREAMseq trial showed a clear overall survival advantage for immunotherapy first, and the phase 2 SECOMBIT trial was concordant. Targeted therapy still works after immunotherapy, but immunotherapy after targeted therapy underperforms, possibly because progression on BRAF/MEK inhibitors is rapid and the tumours are immunologically cold.

## Fields

- Kind: Pairing
- Last checked: 2026-09-07
- Pairs: Immune checkpoint inhibitors + Dabrafenib + trametinib
- Type: sequence
- Rationale: Immunotherapy responses are durable and can be curative; BRAF/MEK responses are fast but nearly always temporary. Using the durable option first preserves the fast option as a rescue.
- Evidence: Phase 3 DREAMseq; phase 2 SECOMBIT concordant.

## Sources

- ClinicalTrials.gov NCT02224781: DREAMseq (ECOG-ACRIN EA6134): https://clinicaltrials.gov/study/NCT02224781

## Connected records

- cancers: [Melanoma](https://onco.cc/cancers/melanoma/)
- targets: [BRAF](https://onco.cc/targets/braf/)
- drugs: [Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [Encorafenib](https://onco.cc/drugs/encorafenib/), [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [Nivolumab](https://onco.cc/drugs/nivolumab/)
- trials: [DREAMseq (ECOG-ACRIN EA6134)](https://onco.cc/trials/dreamseq/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)

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