Progression on prior BRAF + MEK inhibitor combination (dabrafenib + trametinib, vemurafen...

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

ID	`RF-PRIOR-BRAFI-MEKI-FAILED`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	None declared
Sources	`SRC-COMBI-D-LONG-2014` `SRC-NCCN-MELANOMA-2025`

Red Flag Origin

Definition	Progression on prior BRAF + MEK inhibitor combination (dabrafenib + trametinib, vemurafenib + cobimetinib, encorafenib + binimetinib). Resistance is typically MAPK-pathway reactivation; rechallenge with same combination after IO interval may yield short-duration responses, but standard next-line is IO (if not given), chemotherapy, or trial.
Clinical direction	de-escalate
Category	prior-therapy-class

Trigger Logic

{
  "any_of": [
    {
      "finding": "prior_brafi_meki_progression",
      "value": true
    },
    {
      "all_of": [
        {
          "finding": "prior_brafi_meki_received",
          "value": true
        },
        {
          "finding": "best_response_to_brafi_meki",
          "value": "PD"
        }
      ]
    }
  ],
  "type": "composite_score"
}

Notes

Melanoma: standard next line is anti-PD1 ± anti-CTLA4 if not previously given (DREAMseq favored IO→BRAFi sequence; for those who got BRAFi+MEKi 1L without IO, IO 2L appropriate). BRAFi-rechallenge after IO-bridge demonstrated in small series (Romano 2018) — short median PFS (~5 mo) but valid for symptomatic palliation. NSCLC BRAF V600E: post-dab+tram PD → docetaxel + ramucirumab or pembrolizumab if PD-L1 positive. CRC BRAF V600E: encorafenib + cetuximab (BEACON doublet) — if progression on this triplet, options very limited (irinotecan-based; trial preferred).

Used By

No reverse references found in the YAML corpus.