Abstract Background In MONARCH 2, abemaciclib plus fulvestrant significantly improved median progression-free survival (PFS, 16.4 vs 9.3 months, hazard ratio [HR] 0.553) and overall survival (OS, 46.7 vs 37.3 months; HR 0.757) compared with placebo plus fulvestrant in hormone receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative) advanced breast cancer (ABC) patients who were endocrine therapy (ET) resistant, regardless of menopausal status. Here, we report findings in the premenopausal subgroup of the MONARCH 2 trial. Methods The premenopausal subgroup included patients with natural menstrual bleeding who received a gonadotropin-releasing hormone agonist at least 4 weeks prior to study treatment start date and for the entire study duration. Of the 669 patients enrolled in the MONARCH 2 trial, 114 were premenopausal (abemaciclib plus fulvestrant, n = 72; placebo plus fulvestrant, n = 42), and were included in this analysis. The primary objective was investigator-assessed PFS and secondary objectives were OS, objective response rate, and safety and tolerability. Exploratory analyses included time to second disease progression (PFS2), time to chemotherapy (TTC), and chemotherapy-free survival (CFS). Results At the primary objective cutoff (February 14, 2017), median PFS was not reached for the abemaciclib plus fulvestrant arm versus 10.52 months for the placebo plus fulvestrant arm (HR 0.415; 95% CI 0.246–0.698). At the pre-specified OS interim cutoff (20-June-2019), median PFS was 28.6 months in the abemaciclib plus fulvestrant arm compared with 10.26 months in the placebo plus fulvestrant arm (HR 0.477; 95% CI 0.302–0.755). A numerical OS benefit was observed with abemaciclib plus fulvestrant compared to fulvestrant alone (HR 0.689; 95% CI 0.379–1.252, median, not reached vs 47.3 months). Improvements were also observed for the exploratory outcomes of PFS2 (HR 0.599), TTC (HR 0.674), and CFS (HR 0.642) with the addition of abemaciclib to fulvestrant. The safety profile was generally consistent with results disclosed previously. Conclusions Results of the premenopausal subgroup in the MONARCH 2 trial were consistent with the improved clinical outcomes observed in the intent-to-treat population. The analysis provides support for the use of abemaciclib plus fulvestrant (with ovarian suppression) as an effective treatment option for premenopausal patients with HR+, HER2- ABC who are ET-resistant. Clinical trial registration: NCT02107703. Registered April 08, 2014- Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02107703 .
