Everolimus added to endocrine therapy provided modest but statistically significant PFS benefit (5.0 vs 4.3 months; HR 0.68) in ER+/HER2- advanced breast cancer post-CDK4/6 inhibitor progression, without demonstrable OS benefit, supporting selective use.
| Evidence tier | B Direct human evidence |
| Study type | 3 - Human Observational |
| Model system | Human (multicenter retrospective cohort) |
| Journal | Breast Cancer Research and Treatment |
| Year | 2026 |
| Peer reviewed | Yes |
| Source | DOI 10.1007/s10549-026-08012-5 · PMID 42429895 |
Multicentre, international, retrospective quasi-experimental study (n=207 women with ER+/HER2- advanced breast cancer after CDK4/6 inhibitor progression). Everolimus + endocrine therapy (n=150) vs endocrine therapy alone (n=57). Median real-world PFS: 5.0 vs 4.3 months (adjusted HR 0.68, 95% CI 0.47-0.99). Time to everolimus failure: 4.2 months. No significant differences in time to chemotherapy or overall survival. Safety profile consistent with prior reports. Median follow-up 31.8 months.
| Intervention | Everolimus (mTOR inhibitor) + endocrine therapy |
| Target | mTORC1 |
| Model | Human |
| Effect | Modest PFS improvement (HR 0.68) in post-CDK4/6i ER+ breast cancer; no OS benefit demonstrated |