A comprehensive real-world analysis of over 3,000 patients across more than 250 US cancer clinics has revealed a significant treatment gap in adjuvant abemaciclib utilization for high-risk early breast cancer, with 60% of eligible patients not receiving this FDA-approved therapy designed to reduce recurrence risk.
The retrospective study, utilizing the nationwide Flatiron Health electronic health record database, examined 3,170 adult patients with hormone receptor-positive (HR+), HER2-negative, node-positive early breast cancer who underwent surgery and initiated adjuvant endocrine therapy between January 2023 and March 2024. All patients met eligibility criteria for adjuvant abemaciclib based on having N1 disease with additional high-risk features or N2/N3 disease.
Significant Underutilization in High-Risk Population
The analysis found that 1,902 patients (60%) did not receive abemaciclib despite meeting clinical guidelines for treatment. The median age of the overall cohort was 62 years, with patients being predominantly female (98%), White (62%), and treated in community settings (83%). Median follow-up was 9 months.
Older patients and those with N1 disease were disproportionately affected by the treatment gap. This finding is particularly concerning given that patients with N1 plus high-risk features have a 2-fold or greater recurrence risk compared to patients with N1 disease without these high-risk features.
The real-world risk of recurrence in patients with node-positive HR+/HER2- early breast cancer is 29% at 5 years when treated with standard adjuvant endocrine therapy alone. Adjuvant abemaciclib plus endocrine therapy has been shown to reduce this risk by approximately 8% at 5 years compared to endocrine therapy alone.
Real-World Treatment Persistence Data
A separate analysis of 354 patients who did receive abemaciclib provided insights into real-world treatment patterns and persistence. These patients, followed for a median of 8.8 months from abemaciclib initiation, demonstrated characteristics that differed from the pivotal monarchE trial population.
The real-world cohort was older and more diverse, with a median age of 56 years and 25.4% being 65 years or older. The population included 12.7% Black patients and 4.0% Asian patients, with most (80.8%) receiving care in community settings. Over half (55.4%) were postmenopausal, and approximately one-third (33.9%) had one or more comorbidities.
Most patients had stage II (41.8%) or III (38.4%) disease, with nodal status N1 (45.2%) or N2 (35.3%). Abemaciclib was initiated at a median of 11.1 months after early breast cancer diagnosis and 6.7 months after breast surgery. The most frequent treatment regimen was abemaciclib plus aromatase inhibitors (91.0%).
High Persistence Rates Demonstrate Tolerability
The persistence analysis revealed encouraging results for treatment tolerability in routine clinical practice. At 3 months, 81.6% of patients remained persistent on abemaciclib therapy, defined as continuing treatment with medication gaps of 60 days or less. An additional 5.6% resumed abemaciclib after interruptions longer than 60 days, while 11.3% discontinued due to adverse effects.
Prior to abemaciclib initiation, most patients had received radiotherapy (96.3%) and chemotherapy (83.1%), with 46.3% receiving neoadjuvant chemotherapy. Most patients (74.0%) had initiated endocrine therapy approximately 1.6 months before starting abemaciclib.
Clinical Implications and Education Needs
The findings highlight a critical gap between evidence-based treatment recommendations and real-world implementation. The study authors noted that older patients, who showed similar efficacy and adverse effect rates as younger patients in the phase 3 monarchE trial, were among those least likely to receive abemaciclib.
The high 3-month persistence rate of 81.6% in the real-world setting suggests that abemaciclib for early breast cancer is well tolerated in routine clinical practice, supporting its feasibility as an adjuvant treatment option across diverse patient populations.
The researchers emphasized that education on recurrence risk and the consistent benefit of adjuvant abemaciclib in the approved node-positive, high-risk early breast cancer population may be crucial for increasing utilization rates and optimizing treatment outcomes to prevent incurable metastatic disease.
