Giredestrant (oral SERD/full ER antagonist) + everolimus extends PFS2 and chemo-free survival post-CDK4/6 in ER+ aBC

Giredestrant (GIRE) is an oral selective estrogen receptor degrader (SERD) and full ER antagonist combined with everolimus (E; mTOR inhibitor) in the Phase III evERA Breast Cancer trial (NCT05306340) in ER+, HER2– advanced breast cancer progressing on/after CDK4/6 inhibitor + endocrine therapy; patients were randomized to GIRE 30mg QD + E 10mg QD vs SOC endocrine therapy (exemestane/fulvestrant/tamoxifen) + E (n=183 vs 190; ESR1m n=102 vs 105). In this exploratory post-progression analysis, median PFS2 was 19.0 vs 13.2 months (HR 0.69; ESR1m 19.0 vs 12.9 months, HR 0.61; ESR1m-not-detected 17.3 vs 12.9 months, HR 0.77), and chemotherapy-free survival improved (CFS HR 0.61 overall; 0.46 in ESR1m; 0.80 in ESR1m-not-detected), with fewer patients receiving an ADC after discontinuation (24.5% vs 31.4% overall). Safety wasn’t detailed in this abstract, but the parent readout reported no unexpected signals—practically, tolerability is still expected to be dominated by the everolimus backbone (e.g., stomatitis/metabolic effects), similar to historical everolimus+ET use (BOLERO-2 everolimus+exemestane improved PFS vs exemestane alone but is limited by toxicity and discontinuations).