MONARCHplus: A phase III trial of abemaciclib plus nonsteroidal aromatase inhibitor (NSAI) or fulvestrant (F) for women with HR+/HER2- advanced breast cancer (ABC)

Abstract

Background

Abemaciclib is an oral, selective CDK4 & 6 inhibitor dosed on a continuous schedule and approved in combination with endocrine therapy (ET) for HR+/HER2- ABC patients (pts) outside of China in more than 50 countries. MONARCHplus evaluated the efficacy and safety of abemaciclib plus ET in predominantly Chinese pts with HR+/HER2- ABC.

Table: LBA25. Summary of PFS and ORR in ITT population

Empty Cell	Cohort A		Cohort B
Empty Cell	Abemaciclib + NSAI (n = 207)	P + NSAI (n = 99)	Abemaciclib + F (n = 104)	P + F (n = 53)
Median PFS(months)	NR*	14.73	11.47	5.59
HR (95% CI)	0.499 (0.346, 0.719)		0.376 (0.240, 0.588)
p-value	.0001		<.0001
ORR (%)	56.0	30.3	38.5	7.5
p-value	<.0001		<.0001

*

NR= not reached.

Methods

MONARCHplus was a randomized-controlled, double-blind phase III trial for postmenopausal women with endocrine sensitive (Cohort A) or endocrine resistant (Cohort B) HR+/HER2- ABC. In Cohort A, pts received abemaciclib (150 mg Q12h)/ placebo (P) + NSAI (anatrozole or letrozole) as first-line ET. In Cohort B, pts received abemaciclib/P + F following progression to ET. Both cohorts were randomized at a 2:1 ratio. The primary objective was PFS in Cohort A with a key secondary objective of PFS in Cohort B. The trial was powered for Cohort A to 80% at 1-sided α=.025 assuming a hazard ratio (HR) of 0.626 in favor of abemaciclib + NSAI, with analyses at 119 and 170 PFS events.

Results

At the pre-specified interim, 119 PFS events were observed in Cohort A (n = 306) and 82 events in Cohort B (n = 157). Abemaciclib +NSAI and abemaciclib + F statistically and significantly improved PFS and ORR (see Table). PFS benefit was consistent within all stratification factors and pre-specified sensitivity analyses. The safety profile for both abemaciclib arms was consistent with previous reports for abemaciclib plus ET and included neutropenia, diarrhea, leukopenia, and anemia as the most frequent adverse events (AEs).

Conclusions

Abemaciclib in combination with NSAI or fulvestrant provided a statistically significant and clinically meaningful improvement in PFS in predominantly Chinese postmenopausal women with HR+/HER2- ABC with no new safety signals observed. The MONARCHplus interim analysis demonstrated benefit consistent with the MONARCH 2 and 3 studies.

Clinical trial identification

NCT02763566.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

All authors have declared no conflicts of interest.