Interim Analysis Updates Adjuvant Abemaciclib Plus Endocrine Therapy Study


Phase 3 monarchE trial assesses distant relapse free-survival, invasive disease-free survival, and overall survival for the treatment of HR-positive/HER2-negative-, node-positive, high-risk early breast cancer.

Updated study results from an interim analysis of adjuvant abemaciclib (Verzenio) plus endocrine therapy (ET) to treat hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative, node positive, high-risk early breast cancer were presented at the San Antonio Breast Cancer Symposium in Texas on December 6, 2022, assessing overall survival (OS), as well as distant relapse-free survival (DRFS) and invasive disease-free survival (IDFS).

Adjuvant abemaciclib plus ET previously showed a significant improvement in DRFS and IDFS for HR-positive/HER2-negative, node positive, high-risk early breast cancer.

The interim results indicate that adjuvant abemaciclib reduces the risk of recurrence, with benefits sustained beyond the 2-year treatment period, further supporting the use of abemaciclib in patients with high-risk HR-positive/HER2-negative early breast cancer, according to study investigator and presenter Stephen Johnston, MA, PhD, FRCP, head of medical oncology, head of the breast unit, professor of breast cancer medicine and consultant medical oncologist at the Royal Marsden NHS Foundation Trust and the Institute of Cancer Research in London, United Kingdom.

Further follow-up is needed to establish whether OS can be improved with abemaciclib plus ET in these patients, he said.

“Duration is an important question. It is the ability to stay on the drug for a defined period that is important,” Johnston said.

In monarchE (NCT03155997), an open-label, phase 3, randomized trial, adults with HR-positive/HER2-negative, node-positive, early breast cancer at a high risk of recurrence with an Eastern Cooperative Oncology Group performance status of 0 or 1 were recruited from 603 sites in 38 countries. Patients were randomly assigned, grouped by menopausal status, previous chemotherapy, and region, to receive standard-of-care ET of physician's choice for up to 10 years with or without abemaciclib 150 mg orally twice a day for a treatment period of 2 years.

For cohort 1, high-risk disease was defined as either 4 or more positive axillary lymph nodes or between 1 and 3 positive axillary lymph nodes and either grade 3 disease or a tumor size of 5 cm or larger. A smaller cohort had participants with between 1 and 3 positive axillary lymph nodes and Ki-67 of at least 20% as an additional risk factor.

This was a prespecified OS interim analysis planned to occur 2 years after the primary-outcome analysis for IDFS. Efficacy was assessed in the intention-to-treat group, while safety was assessed in all treated patients. The study of 5637 patients, more than 99% of whom were women, was conducted between July 17, 2017, and August 12, 2019.

Of the total participants, 2808 were assigned to receive abemaciclib plus ET and 2829 were assigned to receive ET alone. At a median follow-up of 42 months, median IDFS was not reached in either group, and the IDFS benefit previously reported was sustained: HR 0·664 (95% CI 0·578–0·762, nominal p<0·0001).

At 4 years, the absolute difference in IDFS between the groups was 6.4% (85·8% [95% CI 84·2–87·3]) in the abemaciclib plus ET group compared with 79.4% ([77·5–81·1]) in the ET alone group. In the abemaciclib plus ET group, 157, or 5.6%, died compared with 173, or, 6.1%, in the ET alone group.

The most common grade 3 to 4 adverse events (AEs) were neutropenia, leukopenia, and diarrhea. Serious AEs occurred in 433, or 15.5%, of patients receiving abemaciclib plus ET compared with 256, or 9.1%, of 2800 receiving ET. There were 2 treatment-related deaths in the abemaciclib plus ET group from diarrhea and pneumonitis and none in the ET alone group.

“No new safety signals were seen; the majority of adverse events are seen early in the study,” Johnston said. “The safety profile of abemaciclib is considered manageable for these high-risk patients.”

The benefit of adjuvant abemaciclib showed an increase in absolute DRFS and IDFS benefit at 4 years compared with the 2- and 3-year rates seen originally across all subgroups, Johnston said.

The study will continue until there is a final assessment of OS, according to the presentation.

The latest analysis was published in The Lancet.


Johnston S. Abemaciclib plus endocrine therapy for HR+, HER2-, node-positive, high-risk early breast cancer: results from a pre-planned monarchE overall survival interim analysis, including 4-year efficacy outcomes. Presented at: San Antonio Breast Cancer Symposium; Henry B. Gonzalez Convention Center in Texas: December 6, 2022.

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