Table 1 Studies analyzing how baseline ESR1 mutations affect clinical outcomes
| 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 |