Background

In MONARCH 3, a randomized, double-blind, phase 3 trial; continuous dosing of abemaciclib in combination with an AI (anastrozole or letrozole) conferred significant clinical benefit to postmenopausal women with HR+, HER2- ABC. We here report data from an additional 12 months of follow-up in this trial including analysis for clinically prognostic subgroups (Di Leo et al., 2018).

Methods

From the 31 October 2018 data cutoff, exploratory intermediate efficacy parameters including time to subsequent chemotherapy ([TCT] time from randomization to first chemotherapy [CT]) and time to second disease progression ([PFS2] time from randomization to discontinuation date of first post-discontinuation treatment [PDT], or starting date of the secondPDT, or death) were assessed. TCT and PFS2 were analyzed using the Kaplan-Meier method in the intent to treat (ITT) and subgroups previously identified as significantly prognostic.

Results

In the ITT population, updated PFS was 28.2 vs 14.8 months (HR [95% CI]: 0.525 [0.415, 0.665]; p<.0001) in the abemaciclib vs placebo arms, respectively. A higher number of patients discontinued the study in the placebo arm as compared to the abemaciclib arm, thereby starting a PDT. Systemic PDT was received by 178 (54%) patients in the abemaciclib arm and 123 (74.5%) in the placebo arm, of which 93 (28.4%) and 82 (49.7%) received CT respectively. Addition of abemaciclib to AI deferred the initiation of CT both in the ITT (HR [95% CI]: 0.513 [0.380, 0.691]; p<.0001) and in subgroups (Table). PFS2 was prolonged in the abemaciclib arm (HR [95% CI]: 0.637 [0.495, 0.819]; p<.0004). Consistent with the ITT population, PFS2 favored the abemaciclib arm across all subgroups of prognostic factors (Table). Safety profile was generally consistent with previously disclosed results.Table:

326P

Conclusions

Addition of abemaciclib to AI prolonged PFS2 and TCT in the ITT and all prognostic subgroups.

Clinical trial identification

NCT02246621.

Editorial acknowledgement

Medical writing support was provided by Anchal Sood and editorial assistance by Rod Everhart of Syneos Health, and funded by Eli Lilly and Company.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

M. Martín: Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Eli Lilly and Company; Honoraria (self): Taiho Oncology; Honoraria (self): Pharmamar; Honoraria (self): Roche/Genentech. S. Johnston: Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Advisory / Consultancy: Eli Lilly and Company; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Pfizer; Advisory / Consultancy, Research grant / Funding (self): Puma Biotechnology; Speaker Bureau / Expert testimony: Eisai. J. Huober: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Eli Lilly and Company; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy: Hexal; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (self), Advisory / Consultancy: Abbvie. A. Di Leo: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Celgene; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Eisai; Honoraria (self), Advisory / Consultancy: Genomic Health; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Eli Lilly and Company; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Daiichi Sankyo; Advisory / Consultancy: Genentech; Advisory / Consultancy: Ipsen; Advisory / Consultancy, Travel / Accommodation / Expenses: Puma Biotechnology. V.A. Andre: Shareholder / Stockholder / Stock options, Full / Part-time employment: Eli Lilly and Company. H.R. Martin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Eli Lilly and Company. M.C. Hardebeck: Shareholder / Stockholder / Stock options, Full / Part-time employment: Eli Lilly and Company. M.P. Goetz: Honoraria (self): Genomic Health; Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly and Company; Advisory / Consultancy: Biovica; Advisory / Consultancy: Novartis; Advisory / Consultancy: Sermonix; Advisory / Consultancy: Context Pharm; Research grant / Funding (institution): Pfizer. All other authors have declared no conflicts of interest.