Progression on prior EGFR-targeted therapy (osimertinib, erlotinib, gefitinib, afatinib,...

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

ID	`RF-PRIOR-EGFRI-PROGRESSION`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	None declared
Sources	`SRC-NCCN-COLON-2025` `SRC-NCCN-NSCLC-2025`

Red Flag Origin

Definition	Progression on prior EGFR-targeted therapy (osimertinib, erlotinib, gefitinib, afatinib, dacomitinib, amivantamab — for EGFR-mutant NSCLC; cetuximab, panitumumab — for EGFR-WT colorectal). Triggers resistance testing (T790M for 1G/2G EGFRi, C797S/MET-amp/HER2-amp for osimertinib; RAS/BRAF for anti-EGFR mAb in CRC) and selection of resistance-targeted next line.
Clinical direction	de-escalate
Category	prior-therapy-class

Trigger Logic

{
  "any_of": [
    {
      "finding": "prior_egfri_progression",
      "value": true
    },
    {
      "all_of": [
        {
          "finding": "prior_egfri_received",
          "value": true
        },
        {
          "finding": "best_response_to_egfri",
          "value": "PD"
        }
      ]
    }
  ],
  "type": "composite_score"
}

Notes

NSCLC: Post-1G/2G EGFRi PD with T790M+ → osimertinib (AURA3 / FLAURA paradigm); post-osimertinib PD: chemo + amivantamab + lazertinib (MARIPOSA-2) or chemo alone, with re-biopsy looking for C797S, MET amplification (savolitinib + osimertinib trials), HER2 amp (T-DXd activity), small-cell transformation (require platinum-etoposide). CRC: post-cetuximab/panitumumab PD with acquired RAS — anti-EGFR rechallenge after anti-EGFR-free interval (CHRONOS trial); HER2 amp (trastuzumab + tucatinib per MOUNTAINEER); BRAF V600E (encorafenib + cetuximab per BEACON).

Used By

No reverse references found in the YAML corpus.