Adjuvant Abemaciclib Combined with Endocrine Therapy (ET) in Early Breast Cancer: Updated Results from MonarchE

Abstract

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
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Published: October 14, 2021 DOI: https://doi.org/10.1016/j.annonc.2021.09.015

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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.

	IDFS			DRFS
	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)
Events, n	232	333		191	278
3-Year Rates	88.8%	83.4%		90.3%	86.1%
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)
Events, n	118	172		97	146
3-Year Rates	86.8%	80.8%		88.3%	84.3%
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)
Events, n	104	158		85	135
3-Year Rates	86.1%	79.0%		87.8%	82.6%
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)
Events, n	62	86		50	73
3-Year Rates	91.7%	87.2%		93.1%	89.1

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

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Authors affiliations

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