MONARCH 2: Subgroup analysis of patients receiving abemaciclib + fulvestrant as first-and secondline therapy for HR+, HER2-advanced breast cancer

Background: In MONARCH 2 (M2), abemaciclib (A), an oral selective cyclin dependent kinase 4 & 6 inhibitor, + fulvestrant (F) demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) compared to placebo (P) + F in hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer (ABC). Numerically more pronounced PFS & OS improvement was noted in subgroups (Sub) with visceral (V) disease and primary endocrine resistance. Here we report efficacy data for M2 with respect to 1L and 2L Sub (last line of endocrine therapy [ET] in (neo)adjuvant and metastatic setting, respectively). Methods: M2 (NCT02107703) was a global, randomized, doubleblind Phase 3 trial of A+ F (N = 446) or P + F (N = 223) in women with ET resistant (ETR) HR+, HER2-ABC regardless of menopausal status. Patients (pts) were stratified by site of metastasis (V, bone-only, or other) and resistance to prior ET (primary vs secondary). Exploratory Sub analyses of PFS and OS were conducted among pts in the ITT population with 1L vs 2L. Hazard ratios (HR) were estimated using Cox models with a test of interactions of Sub with treatment performed. Results: At data cut-off (June 20 , 2019), the effect of A + F vs P + F was consistent across 1L (N = 265/133) and 2L (N = 170/86) Sub, with no statistically significant interaction for PFS (p = 0.341) or OS (p = 0.265). For 1L pts, improvements in PFS (HR: 0.57; 95% CI:0.45, 0.73) and OS (HR: 0.85; 95% CI:0.64, 1.14) were observed. Similar efficacy results were observed for 2L pts (PFS: HR: 0.48; [95% CI: 0.36, 0.64]; OS HR: 0.66 [95% CI: 0.46, 0.94]). The numerically largest effects in the 1L population were noted in pts with less favorable prognostic factors such as primary ETR (PFS: HR 0.40 [95% CI: 0.26, 0.63]; OS: HR 0.58 [95% CI:0.35, 0.97]) and V disease (PFS: HR 0.54 [95% CI: 0.39, 0.73]; OS: HR 0.82 [95% CI: 0.57, 1.17]). Conclusions: The statistically significant benefit observed in the M2 study was observed across 1L and 2L patients. In 1L patients (A+F Arm), improvements were observed for PFS and OS with the most pronounced effects noted in patients with less favorable prognostic factors.