Abemaciclib Displays Manageable and Reversible Safety Profile in monarchE PRO Findings for HR+/HER2– Breast Cancer

Patient-reported outcomes demonstrated a manageable safety profile with abemaciclib.

Nadia Harbeck, MD, PhD

Nadia Harbeck, MD, PhD

When administered with endocrine therapy, adjuvant abemaciclib (Verzenio) demonstrated a tolerable as well as reversable safety profile, according to long-term, patient-reported outcome data from the monarchE study (NCT0315597) in patients with hormone receptor–positive, HER2-negative, node-positive, high-risk, early breast cancer.1

In a presentation of the safety data at the 2023 European Society for Medical Oncology Breast Cancer Congress, Nadia Harbeck, MD, PhD, explained that the toxicity profile continues to support the use of abemaciclib and may also serve to counsel patients on treatment expectations. Investigators examined the CDK4/6 inhibitor with endocrine therapy or endocrine therapy alone after a median follow-up of 42 months when all patients had stopped abemaciclib. Further, endocrine therapy was continued for both arms for 3 to 8 years as clinically indicated in patients (n = 5637).

“The overall quality-of-life was quite similar between the arms during the 2-year treatment period,” said Harbeck, who is the head of the Breast Centre and chair for Conservative Oncology at the University of Munich. “It is nice to see that patients had completion rates of over 90% on the study and even around 80% post-study [period].”

To assess outcomes, investigators used PRO instruments as follows: FACT-B, FACT-ES, FACIT-Fatigue. Additionally, a mixed-effects repeated-measures model was used to estimate mean changes from baseline by treatment arm for the instrument summary scores. Assessments were conducted at baseline, 3 months, 6 months, 12 months, 18 months, and 24 months on study treatment. After study treatment, assessments were conducted at 1, 6, and 12 months during the endocrine therapy period.1

Approximately 70% of patients in the doublet arm reported feeling a little bit or not at all bothered by adverse events (AEs) during treatment whereas approximately 25% to 30% of patients either reported being somewhat, quite a bit, or very much bothered. In the endocrine therapy arm numbers were similar; however, slightly more patients were not at all bothered than a little bit bothered during on-study treatment.

“There is no meaningful difference of bother by AEs between the 2 arms,” Harbeck noted. “Everything is completely reversible after completion of abemaciclib.”

During treatment approximately 15% to 20% of patients reported either feeling quite a bit or very much bothered by diarrhea in the abemaciclib arm. Additionally, approximately 30% of patients were not at all bothered and approximately 50% were either somewhat or quite a bit bothered by the diarrhea. After completion of abemaciclib over 75% of patients reported feeling not at all bothered by diarrhea.1

Further, patient-reported fatigue was similar in both arms, with those in the doublet arm experiencing a slight increase in fatigue. Of note, most patients reported fatigue at the baseline assessment.

According to the FACT GP5 measurement “I am bothered by side effects”, at month 24 in the doublet arm 10% of patients were quite a bit or very much bothered and 37% of patients were not at all bothered. At 12-month follow-up, these rates were 8% and 51%, respectively, noting a slight increase in the investigative arm.1

The FACT-ES measurement for “I have diarrhea” showed that 48% of patients receiving abemaciclib were not at all bothered whereas 16% were quite a bit or very much bothered. This represented a noticeable difference as 87% of patients in the endocrine therapy arm reported being not at all bothered and 1% reported being quite a bit or very much bothered by diarrhea. At the 12-month follow-up, numbers were very similar between the 2 arms as 86% of those in the abemaciclib group reported being not at all bothered and 1% reported being quite a bit or very much bothered by diarrhea.

Previous mixed models for repeated measures analyses were consistent with the study results, demonstrating that the addition of abemaciclib to endocrine therapy did not result in meaningful bother differences by AEs.1

“The mature PRO findings from monarchE support a tolerable and reversible toxicity profile for abemaciclib with endocrine therapy in early breast cancer,” Harbeck said. “There are differences for diarrhea because it’s an abemaciclib-associated AE, [otherwise] the addition of abemaciclib to endocrine therapy did not result in clinically meaningful differences in FACT-B, FACT-ES, FACIT-Fatigue, and other individual items.”

Abemaciclib was approved in combination with endocrine therapy by the FDA for the adjuvant treatment of adult patients with hormone receptor–positive, HER2-negative, node-positive, early breast cancer at high risk of recurrence in March 2023. Patients with at least 4 pathologic axillary lymph nodes or 1 to 3 pathologic axillary lymph nodes and/or either grade 3 tumor or a tumor size 50 mm or greater are considered high risk. This indication removed the requirement of testing for Ki-67 expression.2

Disclosures: Dr Harbeck is on the advisory board for AstraZeneca, Daiichi Sankyo, Novartis, Pfizer, Roche, Sandoz-Hexal, Seagen, Aptitude Health, Gilead, and Sanofi.


  1. Harbeck N. Long-term patient-reported outcomes from monarchE: abemaciclib plus endocrine therapy for adjuvant HR+, HER2-, node-positive, high-risk, early breast cancer (EBC). Presented at: 2023 ESMO Breast Cancer Annual Meeting. May 11-13, 2023; Berlin, Germany.
  2. FDA expands early breast cancer indication for abemaciclib with endocrine therapy. FDA. March 3, 2023. May 11, 2023. bit.ly/3I3gT8G
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