VP8-2021: Adjuvant Abemaciclib Combined with Endocrine Therapy (ET): Updated Results from MonarchE
Authors: J. O'Shaughnessy1, P. Rastogi2, N. Harbeck3, M. Toi4, R. Hegg5, J. Sohn6, V. Guarneri7, J. Cortes8, E. Hamilton9, R. Wei10, A. Shahir10, B. San Antonio10, S.C. Nabinger10, S. Tolaney11, M. Martin12, S.R.D. Johnston13
Published: October 14, 2021 DOI: https://doi.org/10.1016/j.annonc.2021.09.015
Background:Adjuvant abemaciclib (CDK4 & 6 inhibitor) combined with ET provides significant and clinically meaningful improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in patients (pts) with HR+, HER2-, node-positive, high risk early breast cancer (EBC). Updated results with a median follow-up of 27 months are presented.
Methods:Pts were randomized (1:1) to receive ET for up to 10 years (yrs) +/- abemaciclib for 2 yrs. Pts had ≥4+ axillary lymph nodes (ALN), or 1-3+ ALN and either grade 3 disease or tumor ≥5 cm (Cohort 1), or 1-3+ ALN and centrally tested Ki-67 ≥20% (Cohort 2). For the ITT (cohort 1+2) and Ki-67 populations, hazard ratio (HR) was estimated using Cox proportional hazard model (data cutoff 1 April 2021). Exploratory analyses estimated the piecewise HR within each yr in the ITT.
Results:With 90% of pts having completed or discontinued the 2-yr study treatment period, the magnitude of IDFS benefit deepened (HR=0.696, 95% CI=0.588, 0.823; nominal p<0.0001) and DRFS benefit was maintained (HR=0.687, 95% CI=0.571, 0.826; nominal p<0.0001). At 3 yrs, absolute improvement in IDFS and DRFS rates were 5.4% and 4.2%, respectively. Abemaciclib benefit deepened during the treatment period (estimated IDFS/DRFS piecewise HRs at yr 0-1 0.795/0.732, yr 1-2 0.681/0.675) and persisted after the 2-yr treatment period (2+ yr IDFS/DRFS piecewise HRs 0.596/0.692). Estimated IDFS rates in the control arm of Cohort 1 (Ki-67 High vs Low) confirmed the prognostic value of Ki-67; however, abemaciclib benefit was consistent regardless of Ki-67 index (table). Overall, AE profile was similar to the prior analysis.
|Abemaciclib + ET||ET||HR (95% CI)||Abemaciclib + ET||ET||HR (95% CI)|
|ITT (Cohort 1+2), N = 5637|
|Patients, N||2808||2829||0.696 (0.588, 0.823)||2808||2829||0.687 (0.571, 0.826)|
|Ki-67 High (Cohort 1+2), N = 2498|
|Patients, N||1262||1236||0.663 (0.524, 0.839)||1262||1236||0.639 (0.494, 0.827)|
|Cohort 1-Ki-67 High, N = 2003|
|Patients, N||1017||986||0.626 (0.488, 0.803)||1017||986||0.599 (0.456, 0.787)|
|Cohort 1-Ki-67 Low, N = 1914|
|Patients, N||946||968||0.704 (0.506, 0.979)||946||968||0.679 (0.473, 0.975)|
Conclusions:The benefit of adjuvant abemaciclib added to ET is strengthened within and beyond the 2-yr treatment period for pts with HR+, HER2-, node-positive, high risk EBC. High Ki-67 was prognostic, but not predictive of abemaciclib benefit. Safety profile remains acceptable for pts with EBC treated with curative intent.
Clinical trial identification:NCT0315
1Baylor University Medical Center, Texas Oncology and US Oncology, Dallas, TX, USA, 2Department of Oncology, NSABP Foundation, Pittsburgh, PA, USA, 3Breast Center, Ludwig-Maximilians-Universität München, Munich, Germany, 4Breast Unit, Kyoto University Hospital, Kyoto, Japan, 5Gynecology and Obstetrics, Gynecological Clinical Service School of Medicine, University of São Paulo, São Paulo, Brazil, 6Division of Medical Oncology, Yonsei Cancer Center, Seoul, Republic of Korea, 7Department of Surgery, Oncology and Gastroenterology Instituto Oncologico Veneto IRCCS, University of Padova, Padua, Italy, 8IOB Institute of Oncology, Quironsalud Group, Hospital Quiron, Barcelona, Spain, 9Breast and Gynecologic Research Program, Sarah Cannon Research Institute, Nashville, TN, USA, 10Oncology, Eli Lilly and Company, Indianapolis, IN, USA, 11Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA, 12Servicio de Oncologia Médica Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain, 13Department of Medicine, Royal Marsden NHS Foundation Trust, London, UK