Results from the phase III evERA trial show that giredestrant plus everolimus significantly extended progression-free survival in advanced ER-positive/HER2-negative breast cancer after progression on a CDK4/6 inhibitor. Among patients with ESR1-mutated tumors, median PFS was 10.0 months versus 5.5 months with standard endocrine therapy plus everolimus, a hazard ratio of 0.38.
In the overall population, the combination also improved PFS, with a median of 8.8 months and a 44% reduction in the hazard of progression. The benefit was seen across most prespecified subgroups, including those with PI3K/AKT/PTEN alterations. Overall survival data are immature, but 18-month estimates favored the experimental arm in both the ESR1-mutated and overall populations.
The trial enrolled 373 patients across 13 countries; 55% had ESR1-mutated tumors. Adverse events were similar between groups, with stomatitis, diarrhea, and anemia most common. The authors noted that the all-oral regimen could reduce treatment burden by avoiding injections and hospital visits. Commentators said the results provide another option for patients with ESR1-mutant disease and support endocrine-based sequencing strategies.