Treatment With Adjuvant Abemaciclib Plus Endocrine Therapy in Patients With High-risk Early Breast Cancer Who Received Neoadjuvant Chemotherapy: A Prespecified Analysis of the monarchE Randomized Clinical Trial

Abstract

Importance: Patients selected to receive neoadjuvant chemotherapy (NAC) are usually those at higher risk of relapse, and there is a need to find better therapeutic options for these patients.

Objective: To determine the efficacy and safety outcomes for patients with hormone receptor (HR)-positive, ERBB2 (formerly HER2)-, high-risk early breast cancer enrolled in the randomized clinical trial monarchE who received NAC.

Design, setting, and participants: The monarchE randomized clinical trial was a multicenter, phase 3, open-label study that evaluated adjuvant treatment with abemaciclib plus endocrine therapy (ET) compared with ET alone in patients with HR+, ERBB2-, and node-positive early breast cancer who were at high risk of recurrence. Patients were recruited between July 2017 and August 2019 from 603 sites in 38 countries. This subgroup analysis was performed with primary outcome data, with a cutoff date of July 8, 2020.

Intervention: Enrolled patients were randomized (1:1) to receive standard of care ET for at least 5 years with or without treatment with abemaciclib (150 mg, twice daily) for 2 years (treatment period) or until criteria were met for discontinuation.

Main outcomes and measures: Prior chemotherapy (NAC vs adjuvant vs none) was a stratification factor in monarchE, and and a prespecified exploratory analysis included outcomes in patients who received NAC. The data presented in this article are from the primary outcome analysis (395 invasive disease-free survival [IDFS] events; cutoff date, July 8, 2020; median follow-up 19 months [IQR, 15.6-23.9 months]). Invasive disease-free survival (the primary end point of monarchE) and distant relapse-free survival (DRFS) were evaluated using the Cox proportional hazard model and Kaplan-Meier method.

Results: Of the 5637 patients (mean [SD] age, 49.9 [10.6] years; 2046 women [99.5%]; 462 Asian [22.8%], 54 Black [2.7%], and 1473 White participants [70.8%]) enrolled in monarchE, 2056 (37%) received treatment with NAC. In this subgroup, treatment with abemaciclib and ET demonstrated clinically meaningful benefit in IDFS (hazard ratio, 0.61; 95% CI, 0.47-0.80) and DRFS (hazard ratio, 0.61; 95% CI, 0.46-0.81), which corresponded with an absolute improvement of 6.6% in 2-year IDFS rates and 6.7% in 2-year DRFS rates. A consistent treatment benefit was observed across subgroups of pathological breast tumor size or number of positive lymph nodes at surgery.

Conclusions and relevance: In the randomized clinical trial monarchE, treatment with adjuvant abemaciclib combined with ET demonstrated a clinically meaningful improvement in IDFS and DRFS for patients with HR+, ERBB2-, node-positive, high-risk early breast cancer who received NAC before trial enrollment.

Trial registration: ClinicalTrials.gov Identifier: NCT03155997.

Conflict of interest statement

Conflict of Interest Disclosures: Drs Wei and Munoz-Fernandez and Mses Forrester, Headley, and Zimmermann reported being full-time employees of Eli Lilly and Company at the time of the study and shareholders of Eli Lilly and Company. Dr Martin reported grants from Roche, Novartis, and Puma and personal fees from Novartis, Pfizer, Daiichi Sankyo, Eli Lilly and Company, SeaGen, and AstraZeneca outside the submitted work. Dr Kim reported grants from Novartis, Sanofi-Aventis, and Dongkook Pharm Co outside the submitted work as well as consulting fees from Novartis, AstraZeneca, Lilly, Dae Hwa Pharmaceutical Co, ISU Abxis, Daiichi-Sankyo, Beigene, Genopeaks, and NeoGene TC. Dr Schenker reported grants from Eli Lilly and Company, BMS, MSD, Roche, Novartis, Regeneron, Sanofi, Merck Serono, AstraZeneca, GlaxoSmithKline, Amgen, Astellas, AbbVie, Bioven, BeiGene, Bayer, Clovis, Gilead, Mylan, Pfizer, PharmaMar, Samsung Pharmaceuticals, and Tesaro outside the submitted work. Dr García-Sáenz reported grants from SeaGen, Gilead, Eli Lilly and Company, AstraZeneca, and Daiichi Sankyo and personal fees from Novartis, Eisai, and MSD outside the submitted work. Dr Papazisis reported honoraria from Novartis, Roche, GSK, MSD, AstraZeneca, Gilead, and Eli Lilly and Company outside the submitted work. Dr Lacko reported personal fees from Eli Lilly and Company, Roche, Pfizer, Egis, Novartis, Mylan, AstraZeneca, MSD, GlaxoSmithKline, Alvogen, the European School of Oncology, Exact Sciences, Teva, and Gilead outside the submitted work. Dr Reeves reported grants from Eli Lilly and Company, the Sarah Cannon Research Institute, Tesaro, TG Therapeutics, Genentech, Celgene, Merck, Bristol Myers Squibb, Boston Biomedical, AstraZeneca, Novocure, Calithera Biosciences, Novartis, Guardant, Acerta Pharma, Rhizen Pharmaceuticals, Takeda, Onconova, Sanofi, CTI Biopharma, Eisai, Janssen, Roche, Myriad Genetics, G1 Therapeutics, Daiichi Sankyo, Arvinas, Cytomix, Sermonix, SeaGen, Taiho, Boehringer Ingelheim, Hutchinson, Macrogenics, Ipsen, Loxo Oncology, Beigene, Acerta, Verastem, Pharmacyclics, AbbVie, Medimmune, Razor Oncology, BioAtla, GlaxoSmithKline, Jiangsu Hengrei, Arcus Biosciences, Amgen, Mirati, Array, Pfizer, Aravive, Ellipses, Immunogen, Karyopharm, Moderna, Thrive, Incyte, Astellas, Ideaya Bio, Appollomics, Tarveda, Ascentage, and Clovis outside the submitted work. Dr Testa reported personal fees from Lilly, Novartis, MSD, Roche, Amgen, Pfizer, and Daiichi-Sankyo and nonfinancial support from United Medical outside the submitted work. Dr Shimizu reported grants from Eli Lilly during the conduct of the study. Dr Denduluri reported research support from the US Oncology Network and being an employee of AstraZeneca outside the submitted work. Dr Johnston reported personal fees from Eli Lilly and Company during the conduct of the study and personal fees from Novartis and AstraZeneca and grants from Pfizer outside the submitted work. No other disclosures were reported.

Figures

Figure.. Kaplan-Meier Curves of Invasive Disease-Free Survival (IDFS)/Distant Relapse-Free Survival (DRFS) in Patients Who Received Neoadjuvant Chemotherapy (NAC)

Kaplan-Meier curves of IDFS (A), DRFS (B), and IDFS/DRFS (inset) to better visualize separation of the curves in patients who received NAC. The inset tables present the number of events per arm, unstratified hazard ratio (HR) in the NAC subgroup, and the 2-year rates in each arm (blue dotted lines). ET indicates endocrine therapy.