Author(s): Miguel Martin, MD, PhD1; Roberto Hegg, MD2; Sung-Bae Kim, MD, PhD3; Michael Schenker, MD, PhD4; Daniela Grecea, MD, PhD5; Jose Angel Garcia-Saenz, MD, PhD6; Konstantinos Papazisis, MD, PhD7; QuChang Ouyang, MD8; Aleksandra Lacko, MD, PhD9; Berna Oksuzoglu, MD10; James Reeves, MD11; Meena Okera, MD12; Laura Testa, MD13; Chikako Shimizu, MD, PhD14; Neelima Denduluri, MD15; Hryhoriy Adamchuk, MD16; Shaker Dakhil, MD17; Ran Wei, PhD18; Tammy Forrester18; Maria Munoz Fernandez, PhD18; Annamaria Zimmermann18; Desiree Headley18; Stephen R. D. Johnston, MD, PhD19
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
Author Affiliations
1Medical Oncology Service, Hospital General Universitario Gregorio Marañon, Universidad Complutense, Centro de Investigación Biomédica en Red-Cáncer, Grupo Español de Investigación en Cáncer de Mama, Madrid, Spain
2Clinica de Pesquisa e Centro São Paulo, São Paulo, Brazil
3Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
4Centrul de Oncologie Sf Nectarie SRL, University of Medicine and Pharmacy Craiova, Craiova, Romania
5Institutul Oncologic “Prof.Dr. Ion Chiricuta” Cluj-Napoca, Cluj-Napoca, Romania
6Medical Oncology Service, Hospital Clinico San Carlos, GEICAM, Madrid, Spain
7Euromedica, General Clinic of Thessaloniki, Thessaloniki, Greece
8Hunan Cancer Hospital, Changsha, China
9Dolnoslaskie Centrum Onkologii, Uniwersytet Medyczny we Wroclawiu, Wroclaw, Poland
10Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey
11Florida Cancer Specialists/Sarah Cannon Research Institute, Fort Myers
12Adelaide Cancer Centre, Kurralta Park, Australia
13Instituto D’Or de Pesquisa e Ensino, São Paulo, Brazil
14National Center for Global Health and Medicine, Tokyo, Japan
15Virginia Cancer Specialists, US Oncology Network, Arlington, Virginia
16Communal Enterprise “Kryvyi Rih oncology dispensary” Dnipr region, Kryvyi Rih, Ukraine
17Cancer Center of Kansas, Wichita, Kansas
18Eli Lilly and Company, Indianapolis, Indiana
19Royal Marsden National Health Service Foundation Trust, London, England
