In MONARCH 2 ( M2 ), Abemaciclib ( Verzenios ), an oral selective cyclin dependent kinase 4 & 6 inhibitor, + Fulvestrant ( Faslodex ) has demonstrated statistically significant improvements in progression-free survival ( PFS ) and overall survival ( OS ) compared to placebo + Fulvestrant 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 with visceral disease and primary endocrine resistance.
Researchers have reported efficacy data for MONARCH 2 with respect to 1L and 2L subgroups ( last line of endocrine therapy in (neo)adjuvant and metastatic setting, respectively ).
MONARCH 2 was a global, randomized, double-blind phase 3 trial of Abemaciclib + Fulvestrant ( N = 446 ) or placebo + Fulvestrant ( N = 223 ) in women with endocrine therapy resistant HR+, HER2- ABC regardless of menopausal status.
Patients were stratified by site of metastasis ( visceral, bone-only, or other ) and resistance to prior endocrine therapy ( primary vs secondary ).
Exploratory sub-analyses of progression-free survival and overall survival were conducted among patients in the intention-to-treat ( ITT ) population with 1L versus 2L.
At data cut-off ( June 20th, 2019 ), the effect of Abemaciclib + Fulvestrant versus placebo + Fulvestrant was consistent across 1L ( N = 265/133 ) and 2L ( N = 170/86 ) subgroups, with no statistically significant interaction for progression-free survival ( p = 0.341 ) or overall survival ( p = 0.265 ).
For 1L patients, improvements in progression-free survival ( hazard ratio, HR: 0.57; 95% CI:0.45, 0.73 ) and overall survival ( HR: 0.85; 95% CI: 0.64, 1.14 ) were observed.
Similar efficacy results were observed for 2L patients ( 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 patients with less favorable prognostic factors such as primary endocrine therapy resistant ( PFS: HR 0.40 [ 95% CI: 0.26, 0.63 ]; OS: HR 0.58 [ 95% CI:0.35, 0.97 ] ) and visceral disease ( PFS: HR 0.54 [ 95% CI: 0.39, 0.73 ]; OS: HR 0.82 [ 95% CI: 0.57, 1.17 ] ).
In conclusion, the statistically significant benefit observed in the MONARCH 2 study was observed across 1L and 2L patients.
In 1L patients ( Abemaciclib + Fulvestrant Arm ), improvements were observed for progression-free survival and overall survival with the most pronounced effects noted in patients with less favorable prognostic factors. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020