LBA17 - Adjuvant abemaciclib plus endocrine therapy for HR+, HER2-, high-risk early breast cancer: Results from a preplanned monarchE overall survival interim analysis, including 5-year efficacy outcomes

Background

Two years (yrs) of adjuvant abemaciclib combined with endocrine therapy (ET) resulted in significant improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) that persisted beyond the 2-yr treatment (tx) period in patients (pts) with hormone receptor positive, human epidermal growth factor receptor 2 negative, node-positive, high-risk early breast cancer (EBC). Here, we report 5-yr efficacy results from a prespecified overall survival (OS) interim analysis.

Methods

Pts were randomized (1:1) to receive ET for at least 5 yrs +/- abemaciclib for 2 yrs (tx period). High-risk EBC was defined as either ≥4 positive axillary lymph nodes (ALN) or 1-3 ALN with Grade 3 disease and/or tumor ≥5 cm (Cohort 1). A smaller group of pts were enrolled with 1-3+ ALN and central Ki67 ≥20% (Cohort 2). The intent-to-treat (ITT) population consisted of Cohort 1 (5120 pts) and Cohort 2 (517 pts). OS in the ITT population was tested for statistical significance in the gated strategy. Hazard ratios (HR) were estimated using Cox proportional hazard model.

Results

In the ITT population, with a median follow-up of 54 months, the benefit of abemaciclib was sustained with a HR of 0.680 (95% CI: 0.599, 0.772) for IDFS and 0.675 (95% CI: 0.588, 0.774) for DRFS. This persistence of abemaciclib benefit translated to continued separation of the KM curves resulting in a 5-yr absolute improvement in IDFS and DRFS rates of 7.6% and 6.7%, respectively, compared with IDFS/DRFS rates of 6.0%/5.3% at 4 yrs and 4.8%/4.1% at 3 yrs. Tx benefit in Cohort 1 was consistent with ITT. No new safety signals were observed. There continued to be fewer deaths in the abemaciclib plus ET arm compared to the ET arm (208 vs 234; HR 0.903; p=0.284); significance was not met.

Conclusions

At the pivotal 5-yr mark for adjuvant EBC trials, abemaciclib plus ET continued to reduce the risk of developing invasive and distant disease recurrence well beyond the completion of tx. The increasing absolute improvement at 5 yrs is consistent with a carryover effect and further supports the use of abemaciclib in pts with high-risk EBC. OS data are evolving in favor of abemaciclib arm, and follow-up continues.

Clinical trial identification

NCT03155997.

Editorial acknowledgement

Monique Mendonca, employee of Eli Lilly and Company, provided medical writing support and editorial assistance.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

N. Harbeck: Financial Interests, Personal, Speaker’s Bureau, Fees for Non-CME Services Received Directly from Commercial Interest or their Agents: Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Seagen; Financial Interests, Personal, Advisory Board, Consulting Fees: AstraZeneca, Daiichi Sankyo, Eli Lilly, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, Seagen; Financial Interests, Personal, Research Funding, Contracted Research: Roche; Financial Interests, Personal, Writing Engagement, Third-party writing assistance for this abstract, furnished by Sunaina Indermun, BPharm, PhD, of Health Interactions: Roche; Financial Interests, Personal, Stocks or ownership: WSG. J. O'Shaughnessy: Financial Interests, Personal, Advisory Board, Consulting Fees: AbbVie, Agendia, Amgen, AstraZeneca, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Eisai, Eli Lilly, F. Hoffmann-La Roche Ltd, G1 Therapeutics, Genentech, Genomic Health, Genzyme, Grail, Heron, Immunomedics, Ipsen, Merck, Myriad, Novartis, Odonate, Pfizer, Pierre Fabre, Prime Oncology, Puma, Roche, Samsung, Sandoz, Sanofi, Seagen, Syndax, TheraLink; Financial Interests, Personal, Research Funding, Contracted Research: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Writing Engagement, Third-party writing assistance for abstract, furnished by Laura Pérez-Pachón, MSc, PhD, of Health Interactions: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Speaker’s Bureau, Fees for Non-CME Services Received Directly from Commercial Interest or their Agents: Gilead; Financial Interests, Personal, Other, Honoraria: Grail, Heron, Ipsen, Roche, Samsung. F. Boyle: Financial Interests, Personal, Advisory Board: Eli Lilly and Company, Novartis, Gilead. J. Cortés: Financial Interests, Personal, Advisory Board: Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck SHARP& DOHME, GSK, LEUKO, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, Hibercell, Menarini, BioInvent, Gemoab, Gilead, Zymeworks, Reveal Genomics; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp & Dohme, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, Guardanth health, Merck Sharp&Dohme, Queen Mary University of London, Pfizer, Piqur Therapeutics, Puma B; Financial Interests, Personal, Other, Consulting/advisor: Expres2ion Biotechnologies; Financial Interests, Personal, Stocks/Shares: MedSIR, Nektar Therapeutics; Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo, Pfizer, Gilead, AstraZeneca. 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Johnston: Financial Interests, Personal, Advisory Board, Consulting Fees: AstraZeneca, Eli Lilly, Pfizer, Sanofi Genzyme; Financial Interests, Personal, Speaker’s Bureau, Fees for Non-CME Services Received Directly from Commercial Interest or their Agents: AstraZeneca. All other authors have declared no conflicts of interest.