In this network meta-analysis of treatment after progression on a CDK4/6i in patients with ER + MBC, we found that in HER2-low tumors, trastuzumab deruxtecan and sacituzumab govitecan showed similar efficacy (PFS and OS), with higher toxicity for sacituzumab govitecan, driven by neutropenia and diarrhea. This evidence concerns the gene ESR1 and neutropenia.