The following article features coverage from the European Society for Medical Oncology 2020 virtual meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Administration of the CDK4/6 inhibitor, abemaciclib, in combination with standard endocrine therapy to patients with high-risk, hormone receptor-positive, HER2-negative, early-stage breast cancer following completion of primary treatment was associated with an approximately 25% reduction in the risk of developing a recurrence of invasive disease, according to results of a preplanned interim analysis of a phase 3 study. These findings were presented at the European Society of Medical Oncology (ESMO) Virtual Congress 2020 and simultaneously published in the Journal of Clinical Oncology.1,2

Despite high rates of cure in patients with early-stage invasive breast cancer treated with standard therapies, such as chemotherapy, radiation therapy, and endocrine therapy, a substantial minority of patients with disease characterized by high-risk features, such as 4 or more positive lymph nodes, histologic grade 3 disease, and large tumor size, will experience disease recurrence. Hence, there is a need for new therapeutic approaches in this setting.

Abemaciclib plus endocrine therapy in the adjuvant setting is was explored based on its efficacy and safety in the metastatic setting in this breast cancer subtype.

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This study was an open-label phase 3 trial (monarchE; Identifier: NCT03155997) in which adult patients with high-risk, early-stage, hormone receptor-positive, HER2-negative invasive breast cancer were randomly assigned in a 1:1 ratio to receive adjuvant endocrine therapy either alone or in combination with the CDK4/6 inhibitor, abemaciclib, with the latter agent administered for 2 years following completion of primary therapy (that must have included surgery). 

High-risk disease was characterized by 4 or more positive lymph nodes, or 1 to 3 positive lymph nodes in the setting of a tumor of at least 5 cm, grade 3 or centrally confirmed Ki-67 expression of at least 20% in untreated breast tissue.

The primary study endpoint was invasive disease-free survival (IDFS), with secondary study endpoints including distant relapse-free survival (DRFS), overall survival (OS), and safety.

The 5637 patients in the intention-to-treat (ITT) population were stratified according to prior chemotherapy, menopausal status, and region of treatment. Choice of standard endocrine therapy was based on physician choice.

The median patient age was 51 years, more than 99% of patients were female, and nearly 95% had received either neoadjuvant (37%) or adjuvant chemotherapy (approximately 58%) at baseline.

At a median follow-up of 15.5 months, there was a significantly higher rate of 2-year IDFS in patients receiving abemaciclib plus endocrine therapy (92.2%) compared with endocrine therapy alone (88.7%), with a hazard ratio (HR) for IDFS of 0.747 (95% CI, 0.598-0.932; P =.0096).

Furthermore, this benefit was observed across all prespecified subgroups, including whether patients had received prior chemotherapy or not, and whether they were classified as pre- or postmenopausal.

Similarly, 2-year DRFS was 93.6% for patients treated with the combination vs 90.3% for those receiving endocrine therapy alone, with a HR for DRFS of 0.717 (95% CI, 0.559-0.920). Thus, the risk of recurrence was reduced by 28.3%. This represents a 3.3% absolute difference. According to the presentation slides, “the greatest reduction in distant metastases was to the liver and bone.”

Regarding safety, no new safety signals were associated with administration of abemaciclib in the adjuvant setting compared with its US Food and Drug Administration (FDA)-approved use in combination with endocrine therapy in patients with advanced hormone receptor-positive, HER2-negative disease.3

Specifically, grade 3 or higher diarrhea, neutropenia, and leukopenia were more common in patients treated with combination therapy. In addition, the incidences of venous thrombotic events, interstitial lung disease and febrile neutropenia, AEs of interest, were more frequent in patients treated with abemaciclib, but low in both study arms. Interestingly, the frequency of all-grade arthralgia and hot flushes were lower in the combination arm compared with endocrine therapy alone. The treatment discontinuation rates due to adverse events in the abemaciclib and control arms were 16.6% and 0.8%, respectively.

In his concluding remarks, presenter Stephen R. Johnston, MD, professor of breast cancer medicine at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, United Kingdom, stated that “abemaciclib is the first CDK4/6 inhibitor to show a significant improvement in IDFS when combined with endocrine therapy in patients with hormone-positive early-breast cancer.”1

According to an ESMO press release on the findings from this study, Giuseppe Curigliano, MD, PhD, associate professor of medical oncology at the University of Milan, Italy, and chair of the ESMO Guidelines Committee, noted that “for the future it will be important to understand if we can potentially spare chemotherapy in this group of patients treated with a CDK4/6 inhibitor. This would need to be investigated in a [randomized] clinical trial.”4

Disclosures: Research funding for this study was provided by Eli Lilly and Co. Some of the presenters reported financial relationships with the pharmaceutical industry. For a full list of disclosures, please refer to the original abstract.

Read more of Cancer Therapy Advisor‘s coverage of the ESMO Virtual Congress 2020 by visiting the conference page.


  1. Johnston SRD, Harbeck N, Hegg R, et al. Abemaciclib in high risk early breast cancer. Presented at: European Society of Medical Oncology (ESMO) Virtual Congress 2020; September 19-21, 2020. Abstract LBA5_PR.
  2. Johnston SRD, Harbeck N, Hegg R, et al. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2−, node-positive, high-risk, early breast cancer (monarchE). J Clin Oncol. Published online September 20, 2020. doi:10.1200/JCO.20. 02514
  3. Abemacicib (Verzenio®) [package insert]. Indianapolis, IN: Eli Lilly and Co.; 2020.
  4. European Society of Medical Oncology (ESMO).  First new drug in years reduces recurrence in high-risk hormone receptor positive early breast cancer [press release]. Published September 20, 2020. Accessed September 20, 2020.