Core rule: sequence by mechanism and toxicity overlap, not alphabetically.
| Combination | Timing | Comment |
|---|---|---|
| Chemotherapy → Endocrine | Standard adjuvant for breast | Cytotoxics first, then endocrine for maintenance |
| Endocrine → Chemotherapy | Only in hormone-resistant or visceral-crisis cases | |
| CDK4/6 + AI/SERD | Concurrent | Requires CBC + LFT monitoring q 2 wk first 2 mo |
| mTOR (Everolimus) + AI | Concurrent second-line | Stomatitis common → prophylactic steroid mouthwash |
| PI3K (Alpelisib) + Fulvestrant | Concurrent for PIK3CA-mutated ER+ disease | Monitor glucose, rash |
| ADT + Docetaxel | Concurrent in high-volume mHSPC | OS gain ~ 13 mo; neutropenia risk |
| ADT + Abiraterone / AR antagonist | Sequential or overlapping per trial | Check BP, K⁺, LFTs |
Never overlap two endocrine classes with the same target (e.g., AI + SERD) — no efficacy, ↑ toxicity.
