The safety and efficacy of abemaciclib will be examined in patients with hormone receptor–positive, HER2-positive, node-positive, high-risk early breast cancer who have completed standard adjuvant HER2-targeted treatment as part of the phase 3 eMonarcHER trial.
The safety and efficacy of the CDK4/6 inhibitor abemaciclib (Verzenio) will be examined in patients with hormone receptor–positive, HER2-positive, node-positive, high-risk early breast cancer who have completed standard adjuvant HER2-targeted treatment as part of the phase 3 eMonarcHER trial (NCT04752332).1
HER2-positive breast cancer represents about 25% of all early-stage breast cancer cases. In the absence of adjuvant systemic therapy, those with HER2-positive disease tend to have a poor prognosis and a high mortality rate. The emergence of neo/adjuvant HER2-targeted therapies have resulted in improved outcomes for patients with early-stage disease, but a subgroup of this population will still experience recurrence of invasive disease following completion of standard neo/adjuvant treatment.
As such, the treatment of patients with high-risk disease continues to be an unmet need. Some of the characteristics that may put a patient at increased risk for recurrence can include the presence of axillary lymph node involvement at the time of diagnosis, a large primary invasive tumor, high histologic grade, and pathological residual disease following neoadjuvant therapy.
Abemaciclib, a potent CDK4/6 inhibitor, has been approved on a global scale for use as a monotherapy and in combination with endocrine therapy in patients with hormone receptor–positive, HER2-negative, advanced or metastatic breast cancer based on data from the MONARCH 1 (NCT02102490), MONARCH 2 (NCT02107703), and MONARCH 3 (NCT02246621) trials.2-4
Moreover, data from the phase 3 monarchE trial (NCT03155997) showed that when abemaciclib is combined with adjuvant endocrine therapy, it significantly improved invasive disease-free survival (IDFS) in patients with hormone receptor–positive, HER2-negative, node-positive, high-risk, early breast cancer (HR, 0.75; 95% CI, 0.60-0.93; P = .01).5 Abemaciclib has also been shown to have activity in cell lines and animal models.6
In the global, randomized, double-blinded, placebo-controlled eMonarcHER trial, investigators set out to examine how well abemaciclib performs in patients with early breast cancer who are receiving hormone therapy following surgery.
To be eligible for enrollment, patients needed to be at least 18 years of age; have confirmed hormone receptor–positive, HER2-positive, early invasive disease; and have undergone definitive surgery of the primary breast tumor with clean margins and/or radiation per study protocol and local guidelines.
Patients needed to have high risk disease that was defined based on initial therapy. If patients received neoadjuvant treatment, they had to have residual axillary nodal disease at definitive surgery. If patients had definitive surgery up front, patients had to have at least 4 positive pathological axillary lymph nodes (pALNs) or 1 to 3 positive pALNs and histologic grade 3 and/or primary invasive tumor size of 5 cm or bigger.
Patients also needed to have completed 9 to 12 months of standard HER2-targeted therapy. If they had received neoadjuvant therapy, they had to have completed neoadjuvant chemotherapy and HER2-targeted treatment for a minimum of 4 cycles and adjuvant ado-trastuzumab emtansine (T-DM1; Kadcyla) for a minimum of 4 cycles with the option to switch over to other trastuzumab (Herceptin)-based therapies thereafter.
If patients underwent up-front definitive surgery, patients needed to have received adjuvant chemotherapy for a minimum of 4 cycles and pertuzumab (Perjeta) plus trastuzumab for a minimum of 4 cycles with the option to switch over to trastuzumab-based therapy thereafter.
If patients previously received treatment with a CDK4/6 inhibitor, immunotherapy, tucatinib (Tukysa), neratinib (Nerlynx), fam-trastuzumab deruxtecan-nxki (Enhertu), or an investigational HER2-targeted therapy in the adjuvant setting, they were excluded. Moreover, patients who received prior endocrine therapy for breast cancer prevention without a diagnosis, those who had a history of breast cancer or venous thromboembolism, and those who had pre-existing serious medical conditions were also excluded. If patients had breast cancer and disease recurrence or distant metastatic disease or inflammatory breast cancer, they could not participate.
The trial plans to enroll approximately 2450 patients with hormone receptor–positive, HER2-positive, high-risk, early breast cancer. Once HER2 therapy is completed, patients will be randomized 1:1 to receive abemaciclib plus endocrine therapy (arm A) or placebo plus endocrine therapy (arm B) for up to 26 cycles. Patients will then go on to receive standard adjuvant endocrine therapy if deemed to be medically appropriate. The follow-up period of the trial is 3 to 8 years.
The primary objective of the research is invasive disease-free survival, as defined by the STEEP criteria, and secondary objectives include overall survival, distant relapse-free survival, incidence of central nervous system metastases as the first site of disease recurrence, safety, patient-reported outcomes, and pharmacokinetics.