BRAF V600E or V600K activating mutation in metastatic / unresectable melanoma — ~40-50% p...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-MELANOMA-BRAF-V600-ACTIONABLE`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-MELANOMA`
Sources	`SRC-CHECKMATE-067-LARKIN-2019` `SRC-COLUMBUS-DUMMETT-2018` `SRC-ESMO-MELANOMA-2024` `SRC-NCCN-MELANOMA-2025`

Red Flag Origin

Definition	BRAF V600E or V600K activating mutation in metastatic / unresectable melanoma — ~40-50% prevalence cutaneous melanoma. Treatment-defining: BRAFi + MEKi doublet (dabrafenib + trametinib, encorafenib + binimetinib — COLUMBUS, vemurafenib + cobimetinib). Sequencing with anti-PD-1 (CheckMate-067, DREAMseq) — IO-first preferred in low-volume disease; BRAF+MEK first in symptomatic / high-LDH disease.
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-MELANOMA-METASTATIC-1L, ALGO-MELANOMA-METASTATIC-2L

Trigger Logic

{
  "any_of": [
    {
      "finding": "braf_v600e_mutation",
      "value": true
    },
    {
      "finding": "braf_v600k_mutation",
      "value": true
    },
    {
      "finding": "braf_mutation",
      "value": "V600E"
    },
    {
      "finding": "braf_mutation",
      "value": "V600K"
    },
    {
      "finding": "braf_v600",
      "value": "positive"
    }
  ],
  "type": "biomarker"
}

Notes

Pyrexia (especially dabrafenib + trametinib) is the dominant BRAF+MEK toxicity — patient education + dose-hold algorithm essential. Encorafenib + binimetinib has lower pyrexia but higher CK elevation. Adjuvant dabrafenib + trametinib (COMBI-AD) for stage III BRAF-mut resected melanoma. Atezolizumab + vemurafenib + cobimetinib (IMspire150) triplet — additional 1L option in select cases. BRAF V600 detection by tissue NGS / PCR; ctDNA acceptable.

Used By

Algorithms

ALGO-MELANOMA-ADJUVANT-1L - ALGO-MELANOMA-ADJUVANT-1L
ALGO-MELANOMA-METASTATIC-1L - ALGO-MELANOMA-METASTATIC-1L
ALGO-MELANOMA-METASTATIC-2L - ALGO-MELANOMA-METASTATIC-2L