Progression on prior CDK4/6 inhibitor + endocrine therapy (palbociclib, ribociclib, abema...

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

ID	`RF-PRIOR-CDK46I-PROGRESSION`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	None declared
Sources	`SRC-ESMO-BREAST-METASTATIC-2024` `SRC-NCCN-BREAST-2025`

Red Flag Origin

Definition	Progression on prior CDK4/6 inhibitor + endocrine therapy (palbociclib, ribociclib, abemaciclib + AI/fulvestrant) in HR+/HER2- metastatic breast cancer. Triggers second-line selection per resistance mechanism: ESR1mut → elacestrant; PIK3CA → alpelisib + fulvestrant; AKT1/PTEN → capivasertib + fulvestrant; BRCA1/2 → PARPi; HER2-low → T-DXd; chemotherapy if endocrine-resistant biology.
Clinical direction	de-escalate
Category	prior-therapy-class

Trigger Logic

{
  "any_of": [
    {
      "finding": "prior_cdk46i_progression",
      "value": true
    },
    {
      "all_of": [
        {
          "finding": "prior_cdk46i_received",
          "value": true
        },
        {
          "finding": "best_response_to_cdk46i",
          "value": "PD"
        }
      ]
    }
  ],
  "type": "composite_score"
}

Notes

Mandatory at progression: ESR1, PIK3CA, AKT1, PTEN, BRCA1/2 testing (liquid biopsy preferred). EMERALD: elacestrant 2L for ESR1mut + CDK4/6i-pretreated, mPFS 3.8 mo vs 1.9 SoC. SOLAR-1: alpelisib + fulvestrant for PIK3CA mutant. CAPItello-291: capivasertib + fulvestrant for AKT-pathway altered. DESTINY-Breast04: T-DXd for HER2-low (IHC 1+/2+ ISH-). Continuing CDK4/6i in 2L with switched endocrine partner (post-MAINTAIN, post-PALMIRA): mixed evidence — modest PFS benefit, generally not preferred over biomarker-driven switch. CDK4/6i rechallenge with abemaciclib (more cytostatic vs cytotoxic profile) considered in oligo-progression after previous ribo/palbo response.

Used By

No reverse references found in the YAML corpus.