Multinational retrospective study of everolimus effectiveness after progression on endocrine therapy plus CDK4/6 inhibitor for ER+/HER2- advanced breast cancer

The multinational retrospective EVERGREEN study evaluated effectiveness and safety of addition of everolimus to endocrine therapy (ET) in women with ER-positive/HER2-negative advanced breast cancer (ER+ HER2- aBC) with disease progression of CDK4/6 inhibitors. The quasi-experimental study included patients who started an immediate next line of ET after progression on CDK4/6 inhibitors, comparing patients exposed to ET plus everolimus in centers where this is standard-of-care with those treated in centers where ET alone is standard-of-care. The primary endpoint was real-world progression-free survival (rwPFS). The study included 207 women (150 everolimus plus ET; 57 ET alone) with a median follow-up of 31.8 months. Baseline characteristics were well balanced, except for a higher number of prior lines in the everolimus plus ET cohort. Median rwPFS was 5.0 months in the everolimus plus ET cohort versus 4.3 months in the ET alone cohort (aHR 0.68; 95% CI 0.47-0.99). Time to everolimus failure was 4.2 months. There were no statistically significant differences in time to chemotherapy or overall survival. The authors conclude that addition of everolimus to ET resulted in a modest clinical benefit for patients with ER+ HER2- aBC who are candidates for ET after CDK4/6 inhibitors. This limited benefit and the toxicity profile warrants careful selection of patients with a favorable risk-benefit profile.