Median follow-up was 52.9 months. mOS was 30.3 months in arm A, 31.43 months in arm B and 22.7 months in arm C (A v C: HR 0.75 [95% CI 0.47, 1.21]; nominal 2-sided p-value 0.243; B v C: HR 0.73 [95% CI 0.46, 1.15]; nominal 2-sided p-value 0.177). In exploratory RNAseq analyses, luminal subtypes were associated with longer PFS (8.6 v 5.4 months [HR 0.54, 95% CI 0.38, 0.79]) and OS (31.7 v. 19.7 months [HR 0.68, 95% CI 0.46, 1]) compared to non-luminal. Updated PFS and safety findings were consistent with the primary analysis (data cutoff 8 Apr 2019).Abemaciclib plus trastuzumab ± fulvestrant numerically improved OS in women with HR+, HER2+ ABC compared to chemotherapy plus trastuzumab with a manageable safety profile.