Abemaciclib ( Verzenios ) is an oral, selective cyclin-dependent kinase 4 & 6 inhibitor, approved for hormone receptor-positive ( HR+ ), human epidermal growth factor receptor 2-negative ( HER2- ) advanced breast cancer ( ABC ) as monotherapy for endocrine refractory disease and with endocrine therapy for initial treatment and after progression on endocrine therapy.
In the MONARCH 2 trial, Abemaciclib + Fulvestrant significantly improved progression-free survival ( PFS ) compared to placebo + Fulvestrant ( median: 16.4 m vs 9.3 m; hazard ratio, HR: 0.553 ) with a generally tolerable safety profile.
Researchers have reported the overall survival ( OS ) results of the prespecified interim.
MONARCH 2 was a global, randomized, double-blind phase 3 trial of Abemaciclib + Fulvestrant or Placebo + Fulvestrant in pre- or perimenopausal ( with ovarian suppression ) and postmenopausal women with advanced endocrine therapy resistant HR+, HER2- advanced breast cancer.
669 patients were randomized 2:1, stratified based on site of metastasis ( visceral, bone-only, or other ) and resistance to prior endocrine therapy ( primary vs secondary ).
Abemaciclib or Placebo 150 mg was dosed Q12H, and Fulvestrant 500 mg was administered per label.
The primary objective was investigator-assessed progression-free survival. Overall survival ( OS ) was a gated secondary endpoint.
The boundary p-value for the interim analysis was 0.0208.
At the prespecified interim analysis, 338 deaths ( 77% of the planned 441 events ) were observed in the ITT population with a median overall survival of 46.7 months for Abemaciclib + Fulvestrant and 37.3 months for Placebo + Fulvestrant ( HR: 0.757; 95% CI: 0.606, 0.945; P = 0.0137 ).
These results met the predefined boundary for significance and are thus definitive.
Overall survival benefit was consistent in all stratification factors; among stratification factors, more pronounced effects were observed in subgroups of visceral disease ( HR: 0.675 ) and primary resistance to prior endocrine therapy ( HR: 0.686 ).
PFS2 ( HR: 0.675; 95% CI: 0.558, 0.816 ) and time to chemotherapy ( HR: 0.622; 95% CI: 0.499, 0.775 ) were also significantly improved.
Safety data were consistent with known Abemaciclib safety profile.
In conclusion, treatment with Abemaciclib plus Fulvestrant has provided a statistically significant and clinically meaningful median overall survival benefit of 9.4 months to pre- or perimenopausal and postmenopausal patients with HR+, HER2- advanced breast cancer who progressed on endocrine therapy with no new safety signals observed. ( Xagena )
Source: ESMO ( European Society of Medical Oncology ) Meeting, 2019