Impact of dose reductions on adjuvant abemaciclib efficacy for patients with high-risk early breast cancer: analyses from the monarchE study

Matthew P Goetz; Irfan Cicin; Laura Testa; Sara M Tolaney; Jens Huober; Valentina Guarneri; Stephen R D Johnston; Miguel Martin; Priya Rastogi; Nadia Harbeck; Ashwin Shahir; Ran Wei; Valérie André; Hope S Rugo; Joyce O'Shaughnessy

doi:10.1038/s41523-024-00639-1

Impact of dose reductions on adjuvant abemaciclib efficacy for patients with high-risk early breast cancer: analyses from the monarchE study

NPJ Breast Cancer. 2024 Apr 26;10(1):34. doi: 10.1038/s41523-024-00639-1.

Authors

Matthew P Goetz¹, Irfan Cicin², Laura Testa³, Sara M Tolaney⁴, Jens Huober^{5

6}, Valentina Guarneri^{7

8}, Stephen R D Johnston⁹, Miguel Martin¹⁰, Priya Rastogi¹¹, Nadia Harbeck¹², Ashwin Shahir¹³, Ran Wei¹⁴, Valérie André¹⁴, Hope S Rugo¹⁵, Joyce O'Shaughnessy¹⁶

Affiliations

¹ Department of Oncology, Mayo Clinic, Rochester, MN, USA. goetz.matthew@mayo.edu.
² Istinye University Faculty of Medicine, Istanbul, Turkey.
³ Instituto D'Or de Pesquisa e Ensino (IDOR), São Paulo, Brazil.
⁴ Dana-Farber Cancer Institute, Boston, MA, USA.
⁵ Cantonal Hospital St. Gallen, Breast Centre St. Gallen, St. Gallen, Switzerland.
⁶ Department of Gynecology and Obstetrics, University of Ulm, Ulm, Germany.
⁷ Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
⁸ Istituto Oncologico Veneto IRCCS, Padova, Italy.
⁹ Royal Marsden NHS Foundation Trust, London, United Kingdom.
¹⁰ Hospital General Universitario Gregorio Marañon, Universidad Complutense, CIBERONC, GEICAM, Madrid, Spain.
¹¹ University of Pittsburgh/UPMC, NSABP Foundation, Pittsburgh, PA, USA.
¹² Breast Centre, Department of Gynaecology and Obstetrics, Comprehensive Cancer Centre München, LMU University Hospital, Munich, Germany.
¹³ Loxo@Lilly, Indianapolis, IN, USA.
¹⁴ Eli Lilly and Company, Indianapolis, IN, USA.
¹⁵ University of California San Francisco Hellen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.
¹⁶ Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, TX, USA.

Abstract

In monarchE, adjuvant abemaciclib significantly improved invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS), with sustained benefit beyond the 2-year treatment period. Abemaciclib dose reductions were allowed to proactively manage adverse events. Exploratory analyses to investigate the impact of dose reductions on efficacy were conducted. Across the three patient subgroups as defined by relative dose intensity (≤66%, 66-93%, ≥93%), the estimated 4-year IDFS rates were generally consistent (87.1%, 86.4%, and 83.7%, respectively). In the time-dependent Cox proportional hazard model, the effect of abemaciclib was consistent at the full dose compared to being reduced to a lower dose (IDFS hazard ratio: 0.905; 95% confidence interval: 0.727, 1.125; DRFS hazard ratio: 0.942; 95% confidence interval: 0.742, 1.195). These analyses showed that the efficacy of adjuvant abemaciclib was not compromised by protocol mandated dose reductions for patients with node positive, hormone receptor positive, human epidermal growth factor 2-negative, high-risk early breast cancer.