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HR-positive metastatic breast cancer after CDK4/6 inhibitors: lines of therapy

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5 standard-of-care settings across 2 lines and 5 biomarker subgroups. Rows come from the cancer page's standard of care; the grid places each on its line and subgroup.

LineAll comersBRCA / HRDESR1HER2-lowPIK3CA / AKT / PTEN
Third line and beyond···1·
Other settings111·1

Third line and beyond

SubgroupSettingApproachProducts and trialsEvidence
HER2-lowEndocrine-refractory, HER2-low or ultralowTrastuzumab deruxtecan before chemotherapy (DESTINY-Breast06), then sacituzumab govitecan (TROPiCS-02) or datopotamab deruxtecan (TROPION-Breast01) after chemotherapy.97

Other settings

SubgroupSettingApproachProducts and trialsEvidence
All comersNo targetable alterationFulvestrant with abemaciclib (postMONARCH), everolimus with exemestane, or another endocrine agent; giredestrant with everolimus is emerging (evERA).91
BRCA / HRDGermline BRCA carriersOlaparib (OlympiAD) or talazoparib (EMBRACA) in place of chemotherapy.87
ESR1ESR1-mutant disease after a CDK4/6 inhibitorElacestrant (EMERALD), imlunestrant (EMBER-3) or vepdegestrant; where available, a switch to camizestrant at the moment ESR1 appears in plasma while continuing the CDK4/6 inhibitor (SERENA-6).89
PIK3CA / AKT / PTENPIK3CA, AKT1 or PTEN alterationCapivasertib with fulvestrant (CAPItello-291); alpelisib with fulvestrant for PIK3CA (SOLAR-1); inavolisib with palbociclib and fulvestrant for PIK3CA-mutant disease relapsing during or soon after adjuvant endocrine therapy (INAVO120).88

Sequence and caution pairings

Lines and subgroups are parsed from the setting text of each standard-of-care row and can misclassify an unusual phrasing; the row’s own setting is always shown. Guideline chips reflect the NCCN category and ESMO-MCBS grade recorded on the cancer page, checked on its stated date. Not medical advice.