Table 1.

Current Guideline-Preferred First-Line ER+/HER2– Advanced Breast Cancer Regimens.

ABC 5 * [30]	ESMO 2021 * [31]	NCCN (Version 3.2023) [33]
CDK4/6i combined with ET (AI or FUL) ESMO-MCBS v1.1 † scores: RIB + LET 1L (post): 4 PAL + LET 1L (post): 3 ABE + AI 1L (post): 3 RIB + FUL 1L, 2L (post): 4 ABE + FUL 1L, 2L (post): 4 RIB + ET 1L (pre): 5	CDK4/6i combined with ET (AI or FUL): AI preferred if did not relapse on AI or relapsed ≥12 months of stopping adjuvant AI; otherwise, FUL preferred Comorbidities or performance status that precludes use of CDK4/6i combinations: ET alone See ABC 5 column for ESMO-MCBS scores	AI + CDK4/6i AI + RIB (category 1) AI + ABE (category 2A) AI + PAL (category 2A) FUL + CDK4/6i FUL + RIB (category 1) FUL + ABE (category 1) FUL + PAL (category 2A)

* ABC and ESMO note the lack of head-to-head comparisons between CDK4/6i; direct cross-trial comparisons are not possible due to heterogeneous inclusion criteria. ^† Based on online scores at https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards accessed 1 February 2023. Cancer therapies are scored from 1–5 for therapies in the non-curative setting, where a score of 4 or 5 is considered to provide a substantial amount of clinical benefit. 1L, first line; 2L, second line; ABC, advanced breast cancer; ABE, abemaciclib; AI, aromatase inhibitor; CDK4/6i, cyclin dependent kinase 4/6 inhibitor; ET, endocrine therapy; ESMO, European Society for Medical Oncology; FUL, fulvestrant; LET, letrozole; MCBS, magnitude of clinical benefit scale; NCCN, National Comprehensive Cancer Network; NSAI, nonsteroidal aromatase inhibitor; PAL, palbociclib; pre, premenopausal; post, postmenopausal; RIB, ribociclib.