Risk Factors Linked to Discontinuation of Adjuvant Abemaciclib in HR+/HER– Breast Cancer


Several key risk factors seen in the monarchE trial of adjuvant abemaciclib could help early monitoring of patients with hormone receptor–positive, HER2-negative, node-positive high-risk early breast cancer to prevent discontinuation.

Patients who discontinued adjuvant abemaciclib (Verzenio) were associated with several risk factors based on analysis of the phase 3 monarchE trial (NCT03155997) examining in patients with hormone receptor­–positive, HER2-negative, node-positive high-risk early breast cancer, indicating that treatment monitoring and early dose adjustments were critical for certain patients, according to data presented in a poster at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.

Characteristics such as patient age of 65 year or older, enrollment in either North America or Europe, an ECOG performance status of 1, postmenopausal status, 1 to 3 positive lymph nodes, and 4 or more pre-existing co-morbidities were found to be associated with treatment discontinuation in the exploratory analysis.

“The differentiation in discontinuation between subgroups within each factor started early on treatment and continued to separate during the 2-year treatment period,” the study authors who were led by Sara M. Tolaney, MD, MPH, chief of the Division of Breast Oncology and associate director of the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute as well as associate professor of medicine at Harvard Medical School in Boston, Massachusetts, wrote in their poster.

monarchE was an open-label randomized study that compared adjuvant abemaciclib at 150 mg twice daily plus endocrine therapy for 2 years vs endocrine therapy alone in the indicated patient population. Endocrine therapy could continue in the year’s following as clinically indicated. Patients had high-risk disease defined by 4 or more positive axillary lymph nodes or 1 to 3 positive axillary lymph nodes and either a 5 cm or larger tumor, histologic grade 3 disease, or centrally tested Ki67 at or above 20%.

Time to discontinuation (TTD) in the abemaciclib-treated patients was time from the first dose to discontinuation of active therapy. A discontinuation event was due to any reason other than disease progression.

Factors of age, region, ECOG performance status, menopausal status, number of positive lymph nodes, and pre-existing comorbidities were associated with TTD­ by both univariate analysis (P <.05) and multivariate analysis (entry and retaining P <.05).

In the multivariate analysis for geographic region, the North America/Europe group was significantly associated with TTD vs Asia (HR, 0.674; 95% CI, 0.543-0.837) and other regions (HR, 0.670; 95% CI, 0.555-0.808; P <.0001). Rates of discontinuation at the 6-, 12-, and 24-month time points were 16.5%, 23.5%, and 32.4% for North America/Europe; 10.3%, 13.9%, and 18.5% for Asia; and 12.1%, 15.8%, and 21.5% for other regions

On multivariate analysis, factors such as post-menopausal vs pre-menopausal status (HR, 1.521; 95% CI, 1.275-1.816; P <.0001), ages 65 years and older vs younger than 65 years (HR, 1.891; 95% CI, 1.576-2.270; P <.0001), and baseline ECOG performance status of 0 vs 1 (HR, 0.799; 95% CI, 0.660-0.968; P <.022) were all significantly associated with TTD. Discontinuation rates for patients by pre- and post-menopausal status were 9.3% vs 17.7%, respectively, at 6 months, 12.8% vs 24.6% at 12 months, and 18.4% vs 33.0% at 24 months. Discontinuation rates for patients younger and older than 65 years were 11.6% vs 27.6%, respectively, at 6 months, 16.3% vs 36.4% at 12 months, and 22.9% vs 46.8% at 24 months. Comparing discontinuation by ECOG performance status yielded rates of 13.7% for 0 and 15.8% for 1 at 6 months, 18.7% vs 24.0% at 12 months, and 25.2% vs 34.6% at 24 months.

By number of positive nodes, 1 to 3 were significantly associated with TTD by multivariate analysis vs 4 to 9 (HR, 0.799; 95% CI, 0.679-0.940) and 10 or more (HR, 0.633; 95% CI, 0.513-0.782; P <.001). For patients with 1 to 3 positive nodes, rates of discontinuation at 6, 12, and 24 months were 16.1%, 22.3%, and 30.6%. In those with 4 to 9 positive nodes, the rates were 13.2%, 17.9%, and 24.7%. With 10 or more nodes, discontinuation rates were 11.6%, 16.8%, and 22.4%.

Using no pre-existing conditions as a comparison, the presence of 1 to 3 (HR, 1.194; 95% CI, 0.927-1.538) or 4 or more (HR, 1.531; 95% CI, 1.181-1.986) unique conditions at baseline was also significantly associated with TTD (P <.007). For patients with 0 pre-existing conditions, discontinuation at 6, 12, and 24 months occurred in 9.7%, 12.1%, and 16.8%. In those with 1 to 3 conditions, the rates were 12.8%, 17.7%, and 23.9%. With 4 or more conditions, discontinuation rates were 18.0%, 25.5%, and 35.2%.

Investigators noted that differentiation in discontinuation rates occurred early during the course of treatment and separated during the 2-year treatment period.


Tolaney SM, Johnston SRD, Wei R, et al. Adjuvant abemaciclib for high-risk early breast cancer (EBC): Factors increasing the rate of treatment discontinuations in monarchE. J Clin Oncol. 2022;40(suppl_16):527. doi: 10.1200/JCO.2022.40.16_suppl.0527

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