Abemaciclib Plus Anastrozole: Promising Signals Reported in Phase II Study of Early Breast Cancer

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As neoadjuvant therapy, abemaciclib alone or in combination with anastrozole achieved strong signals of anticancer activity in postmenopausal patients with hormone receptor–positive, HER2-negative breast cancer in the neoMONARCH phase II study.1 Abemaciclib alone or in combination with anastrozole had robust anticancer effects on cell-cycle proliferation and the immune system.

Abemaciclib is being developed for metastatic breast cancer. Based on these promising preliminary findings, abemaciclib will continue to be developed in patients with early-stage breast cancer.

The majority of patients who received abemaciclib and anastrozole experienced an objective response, and there were no new safety signals when the drug was combined with anastrozole.
— Sara Hurvitz, MD

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“The study met its primary endpoint. Tissue analysis is a novel aspect of this trial,” said lead investigator Sara Hurvitz, MD, Director of the Breast Oncology Program at UCLA’s Jonsson Comprehensive Cancer Center, at the 2016 San Antonio Breast Cancer Symposium. “The majority of patients who received abemaciclib and anastrozole experienced an objective response, and there were no new safety signals when the drug was combined with anastrozole.”

Abemaciclib is one of several cyclin-dependent kinase (CDK) 4/6 inhibitors in clinical development. Palbociclib (Ibrance), another CDK4/6 inhibitor, is approved for the treatment of breast cancer, and approval is expected soon for ribociclib.

Study Details

The neoMONARCH trial enrolled 220 postmenopausal women with hormone receptor–positive, HER2-negative breast cancer suitable for neoadjuvant endocrine therapy (stages II, IIIA, or IIIB).1 A core biopsy was obtained at baseline, and then patients were randomized to one of three treatment arms: anastrozole at 1 mg, abemaciclib at 150 mg every 12 hours plus anastrozole at the same dose, or abemaciclib alone at the same dose. They were treated for 14 days and had another core biopsy at that time.

The primary endpoint of the trial was to compare the change in expression of Ki67 (a marker of tumor cell proliferation) after 2 weeks of therapy. Adjuvant therapy studies have strongly suggested that Ki67 is a potential surrogate marker for disease-free survival after adjuvant endocrine therapy, Dr. Hurvitz explained.

After the 2-week assessment of Ki67 expression, patients continued on the combination of abemaciclib and anastrozole for 14 more weeks and had a third core biopsy, at which time they could undergo surgery. Loperamide was given prophylactically every 12 hours for the first 28 days of treatment with abemaciclib to prevent diarrhea.

Primary Endpoint Met

The study met its primary endpoint. The geometric mean change in Ki67 expression in each arm was significant for both abemaciclib-containing arms vs anastrozole: –92.6 for abemaciclib plus anastrozole, ­–90.6% for abemaciclib alone vs –63.2% for anastrozole (P < .001 for both arms vs anastrozole).

Combination Neoadjuvant Therapy for Early Breast Cancer

  • The combination of the CDK4/6 inhibitor abemaciclib plus anastrozole is promising for the treatment of hormone receptor–positive, HER2-negative early breast cancer.
  • Correlative studies show positive effects on tumor cell proliferation and immune activation.
  • This combination therapy will be studied in the adjuvant setting.

Both abemaciclib arms achieved significantly superior cell-cycle arrest at 2 weeks compared with anastrozole alone (P < .001). In 106 patients who completed treatment with abemaciclib plus anastrozole, the radiologic response rate was 54.7%, and the objective response rate measured with calipers was 56.4%.

Based on slides of individual patients who responded to abemaciclib, histologic changes leading to well-differentiated cells were evident after 15 days of treatment, and these changes are in parallel with the decrease observed in Ki67 expression. Furthermore, at the end of 4 months of treatment, cyototoxic T cells were infiltrating the tumor, but there was no evidence of regulatory T-cell infiltration.


The most common adverse effect associated with abemaciclib was diarrhea (55.2%, mostly grades 1 and 2). In this trial, prophylactic loperamide was successful, and only 4% of patients had grade 3 diarrhea. Neutropenia of all grades was observed in 61% of patients; grades 3 and 4 were seen in 8.2%. “We are not seeing any delays in surgery due to toxicity,” Dr. Hurvitz commented.

Abemaciclib is distinct from palbociclib and ribociclib in that it can be given continuously, whereas the other two CDK4/6 inhibitors are given 3 weeks on and 1 week off, during which time there is concern about rebound in cell proliferation, she explained.

This large study in early breast cancer has “rich histologic evaluation, and the data will become important to us as we move forward in evaluating this drug,” concluded Dr. Hurvitz. ■

Disclosure: Dr. Hurvitz has received research funding from Amgen, Bayer, Boehringer Ingelheim, Genentech, GlaxoSmithKline, Lilly, Novartis, Dignitana, Pfizer, Roche, BioMarin, Merrimack, OBI Pharma, Puma Biotechnology, and Medivation.


1. Hurvitz S, Martin M, Fernández Abad M, et al: Biological effects of abemaciclib in a phase 2 neoadjuvant study for postmenopausal patients with hormone receptor–positive, HER2-negative breast cancer. 2016 San Antonio Breast Cancer Symposium. Abstract S4-06. Presented December 8, 2016.

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