Several baseline factors were associated with an increased risk for treatment discontinuation in the phase 3 monarchE clinical trial, which assessed adjuvant abemaciclib (Verzenio) in patients with hormone receptor–positive, HER2-negative early breast cancer, according to findings from a multivariate analysis presented during the 2022 American Society of Clinical Oncology Annual Meeting.
Age ≥65 years was the most common variable associated with early discontinuation in patients enrolled in the study, reported Sara M. Tolaney, MD, MPH, Chief, Breast Oncology, Susan F. Sith Center for Women’s Cancers, Dana-Farber Cancer Institute, Boston, MA, and colleagues, in their poster presentation. Additional factors significantly associated with a higher risk for discontinuation in a multivariate model were enrollment in a North American or European Union center, an Eastern Cooperative Oncology Group (ECOG) performance status of 1, postmenopausal status, 1 to 3 positive lymph nodes, and 4 or more preexisting comorbidities.
“These results illustrate the importance of close monitoring along with appropriate interventions, such as dose adjustments, early on treatment to retain patients on abemaciclib treatment,” Dr Tolaney and colleagues noted.
MonarchE was an international phase 3 study that enrolled 5637 patients with pre- and postmenopausal high-risk, hormone receptor–positive, HER2-negative early breast cancer. For purposes of the study, high-risk disease was defined as having ≥4 positive axillary lymph nodes or 1 to 3 axillary lymph nodes and ≥1 of several disease characteristics, including tumor size ≥5 cm, histologic grade 3 disease, and centrally tested Ki67 of ≥20%.
After completing primary therapy, patients were randomized to 150 mg of abemaciclib twice daily, for up to 2 years, plus 5 to 10 years of endocrine therapy (N = 2808), as clinically indicated, or to endocrine therapy alone (N = 2829). Patient stratification factors were previous chemotherapy, menopausal status, and region. Approximately 40% of patients were premenopausal and 58% received adjuvant chemotherapy.
Adjuvant abemaciclib plus endocrine therapy led to a clinically meaningful improvement in reducing the risk for recurrence. However, 25.6% of patients discontinued abemaciclib before completing the 2-year treatment period due to reasons other than recurrence. The exploratory analysis by Dr Tolaney and colleagues evaluated the impact of baseline factors on time to discontinuation for patients treated with abemaciclib.
The investigators found that patients aged ≥65 years were significantly more likely than their younger counterparts to discontinue abemaciclib (hazard ratio [HR], 1.891). This was also the case for postmenopausal versus premenopausal patients (HR, 1.521) and those with ≥4 comorbidities versus none (HR, 1.531).
By contrast, the likelihood of treatment discontinuation was significantly lower for patients with an ECOG performance status of 0 versus 1 (HR, 0.799), those with 4 to 9 or ≥10 positive nodes versus 1 to 3 nodes (HRs, 0.799 and 0.633, respectively), and those treated in Asia or other geographic regions versus North America or Europe (HRs, 0.674 and 0.670, respectively).
Dr Tolaney and colleagues noted that the differences “in discontinuation between subgroups within each factor started early on treatment and continued to separate during the 2-year treatment period.” For example, at 6 months, the highest estimated rates of early discontinuation occurred in patients aged ≥65 years (27.6%), patients with ≥4 comorbidities (18.0%), postmenopausal patients (17.7%), patients treated in North America or the European Union (16.5%), patients with 1 to 3 positive nodes (16.1%), and patients with a baseline ECOG performance status of 1 (15.8%).
At 2 years, patients aged ≥65 years (46.8%), those with ≥4 comorbidities (35.2%), those with a baseline ECOG performance status of 1 (34.6%), postmenopausal patients (33.0%), those treated in North America or Europe (32.4%), and those with 1 to 3 positive nodes (30.6%) were most likely to discontinue abemaciclib.