While many patients with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative early breast cancer will not recur or have distant relapse with standard adjuvant therapies, up to 20% of patients whose cancer has high-risk clinical and/or pathological features may experience distant relapse, many in the first 2 years. MonarchE showed that 2-year treatment with abemaciclib plus endocrine therapy significantly improves the risk on invasive disease-free survival (IDFS) in these patients.
Standard treatment for patients with HR-positive, HER2-negative early breast cancer varies depending on the risk of recurrence but includes combinations of surgery, radiotherapy, adjuvant/neoadjuvant chemotherapy, and endocrine therapy . Although many patients with HR-positive, HER2-negative disease will not experience recurrence or have distant recurrence with standard therapies alone, up to 20% of patients may experience disease recurrence in the first 10 years, often with distant metastases, at which time the disease is incurable. For those patients with high-risk clinical and/or pathologic features, risk of recurrence is even higher, especially during the first few years on adjuvant endocrine therapy. It is therefore critical to optimise adjuvant therapy for these patients to prevent early recurrences and metastases.
Abemaciclib is an oral CDK4/6 inhibitor approved for use in HR-positive, HER2-negative advanced or metastatic breast cancer. Adjuvant treatment with abemaciclib plus endocrine therapy has shown to significantly improve disease-free and overall survival in patients with advanced/metastatic HR-positive, HER2-negative breast cancer .
Corroborating on these results, the phase 3 MonarchE trial evaluates the effect of abemaciclib plus endocrine therapy in patients with HR-positive, HER2-negative early breast cancer. In total, 5,637 patients were enrolled in the study. All patients had high-risk, HR-positive, HER2-negative early breast cancer. High risk was defined as having ≥4 positive nodes, or 1-3 nodes and at least one of the following: tumour size ≥5 cm, histologic grade 3, or central Ki-67 ≥20%. Patients were 1:1 randomised to abemaciclib (150 mg BID for 2 years) plus endocrine therapy or endocrine therapy alone. The primary endpoint was IDFS per STEEP criteria. Secondary endpoints included distant relapse-free survival (DRFS), overall survival, and safety. Prof. Stephen Johnson (Royal Marsden Hospital, UK) presented the results of a pre-planned efficacy interim analysis of the MonarchE trial at 323 IDFS events. A positive study required a 2-sided P-value <0.0264 based on this actual number of IDFS events. Medium follow-up at the interim analysis was 15.5 months in both arms; 12.5% of patients had completed the 2-year period of adjuvant treatment with either abemaciclib plus endocrine therapy of endocrine therapy alone.
Abemaciclib plus endocrine therapy demonstrated a statistically significant improvement in IDFS versus endocrine therapy alone. At the time of the cut-off, there were 136 IDFS events in the abemaciclib arm versus 187 in the placebo-arm (HR 0.747; P=0.0096), corresponding to a 25.3% reduction in the risk of an IDFS event. The 2-year IDFS rates were 92.2% versus 88.7%, respectively. Consistent benefit was seen in all prespecified subgroups. A similar improvement was observed for DRFS: 106 events in the abemaciclib arm versus 152 events in the placebo arm (HR 0.717; P=0.0085), corresponding to a 28.3% reduction in the risk of distant recurrence. The 2-year DRFS rates were 93.6% and 90.3%, respectively. Most distant recurrences were seen in bone (32 in the abemaciclib arm versus 81 in the placebo arm) and liver (29 versus 42). The most frequent adverse events were consistent with the know abemaciclib safety profile: diarrhoea, neutropenia, mostly grade 1 or 2 and decreasing in time.
So, in conclusion, abemaciclib combined with endocrine therapy showed a statistically significant improvement in IDFS and DRFS in patients with high-risk, HR-positive, HER2-negative early breast cancer.
- Cardoso F, et al. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2019;30:1194-1220.
- Sledge GW, et al. The Effect of Abemaciclib Plus Fulvestrant on Overall Survival in Hormone Receptor–Positive, ERBB2-Negative Breast Cancer That Progressed on Endocrine Therapy—MONARCH 2. JAMA Oncol. 2020;6:116-124.
- Johnston SRD, et al. Abemaciclib in high risk early breast cancer. ESMO 2020 Virtual, abstract LBA5.