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Table 1 Studies analyzing how baseline ESR1 mutations affect clinical outcomes

From: ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer

Drugs Study Prior treatment % MUT Results Conclusions
AI, SERD SoFEA
(NCT00253422,
NCT00944918)
ET-resistant
fulvestrant 0%
chemo 0–1 lines
39 PFS, SoFEA + EFECT
ESR1-WT exemestane 4.8 mo, fulvestrant 4.1 mo
ESR1-MUT exemestane 2.4 mo, fulvestrant 3.9 mo (NS vs. WT)
1Y OS, SoFEA + EFECT
ESR1-WT exemestane 79%, fulvestrant 81%
ESR1-MUT exemestane 62%, fulvestrant 80% (NS vs. WT)
ESR1-MUT does not predict response to fulvestrant
AI, SERD EFECT
(NCT00065325)
ET-resistant
chemo 23%
23
SERD FERGI
(NCT01437566)
ET-resistant
fulvestrant 0%
chemo 0–1 lines
37 PFS
ESR1-WT fulvestrant 3.7 mo
ESR1-MUT fulvestrant 3.5–7.4 mo (NS vs. WT)
ESR1-MUT does not predict response to fulvestrant
SERD plasmaMATCH
(NCT03182634)
ET-resistant (median 2 lines)
chemo 66%
CDK4/6i 10%
mTORC1i 21%
100 ORR
ESR1-MUT: 8% (12% if ESR1-MUT was the dominant clone)
PFS
ESR1-MUT: 2.2 mo
Heavily pretreated ESR1-MUT has short PFS on fulvestrant
SERD, CDK4/6i PALOMA-3
(NCT01942135)
ET-resistant
fulvestrant 0%
chemo 34%
25 ORR
ESR1-WT: fulvestrant 8.6%, fulvestrant + palbociclib 19%
ESR1-MUT: fulvestrant 11.7%, fulvestrant + palbociclib 20.4% (NS vs. WT)
PFS
ESR1-WT: fulvestrant 5.4 mo, fulvestrant + palbociclib 9.5 mo
ESR1-MUT: fulvestrant 3.6 mo, fulvestrant + palbociclib 9.4 mo (NS vs. WT)
ESR1-MUT does not predict response to fulvestrant + palbociclib
CDK4/6i PEARL
(NCT02028507)
ET-resistant
fulvestrant 0%
chemo 28%
29 PFS
ESR1-WT: exemestane + palbociclib 9.3 mo
ESR1-MUT: exemestane + palbociclib 5.7 mo (p = 0.06 vs. WT)
ESR1-WT: fulvestrant + palbociclib 7.5 mo
ESR1-MUT: fulvestrant + palbociclib 7.6 mo (NS vs. WT)
OS
ESR1-WT: exemestane + palbociclib 35 mo
ESR1-MUT: exemestane + palbociclib 25 mo (* vs. WT)
ESR1-WT: fulvestrant + palbociclib 30 mo
ESR1-MUT: fulvestrant + palbociclib 27 mo (* vs. WT)
ESR1-MUT does not predict response to fulvestrant + palbociclib
ESR1-MUT predicts resistance to exemestane + palbociclib
CDK4/6i PADA-1
(NCT03079011)
3.2 PFS
ESR1-WT AI + palbociclib not reached
ESR1-MUT AI + palbociclib 17.5 mo (* vs. WT)
ESR1-MUT predicts resistance to AI + palbociclib
CDK4/6i nextMONARCH 1
(NCT02747004)
ET-resistant
chemo 2+ lines
CDK4/6i 0%
41 PFS
ESR1-WT versus ESR1-MUT abemaciclib NS
ESR1-MUT does not predict response to abemaciclib
CDK4/6i, mTORC1i TRINITI-1
(NCT02732119)
ET-resistant
fulvestrant 37%
chemo 8%
CDK4/6i 100%
34 PFS
ESR1-WT: exemestane + everolimus + ribociclib 6.9 mo
ESR1-MUT: exemestane + everolimus + ribociclib 3.5 mo (* vs. WT)
ESR1-MUT predicts resistance to exemestane + everolimus + ribociclib
mTORC1i BOLERO-2
(NCT00863655)
ET-resistant
fulvestrant 17%
chemo 26%
29 PFS
ESR1-WT: exemestane 4.0 mo, everolimus + exemestane 8.5 mo
ESR1-MUT: exemestane 2.8 mo, everolimus + exemestane 5.4 mo (* vs. WT)
ESR1-MUT predicts resistance to exemestane + everolimus
PI3Ki NCT01870505 ET median 2 lines
chemo median 2 lines
20* 16-wk CBR
ESR1-WT: AI + alpelisib 62%
ESR1-MUT: AI + alpelisib 0% (* vs. WT)
ESR1-MUT predicts resistance to AI + alpelisib
  1. All studies except for PADA-1 were retrospective analyses of existing data. Sample sizes and references are in the main text. % MUT: percentage of patients in the analyzed cohort with baseline ESR1-MUT in cfDNA. *: solid sample, not cfDNA. Also notable was that 88% of patients had a baseline PIK3CA mutation in this study