For the first time, an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6) has improved outcomes in patients with early breast cancer when combined with standard endocrine therapy, Stephen Johnston, MD, PhD, and colleagues reported at the ESMO Virtual Congress 2020 (Abstract LBA5_PR). Abemaciclib plus endocrine therapy significantly reduced the risk of an invasive disease–free survival event by 25% vs endocrine therapy alone in the global phase III monarchE trial. Distant recurrences were reduced as well—by 28%.
“The results attest to the efficacy of the drug in having an impact in the early disease setting,” said Dr. Johnston, Professor of Breast Cancer Medicine at the Royal Marsden Hospital NHS Foundation Trust, in a press briefing in advance of the meeting. The prevention of early recurrence and metastasis may reflect the combination’s impact on endocrine resistance in subclinical metastatic disease thought to be present in high-risk patients, he suggested.
Stephen Johnston, MD, PhD
Giuseppe Curigliano, MD
“This is really an important trial,” commented Giuseppe Curigliano, MD, Associate Professor of Medical Oncology at the University of Milan, Italy, and Chair of the ESMO Guidelines Committee. “It will potentially change clinical practice.”
MonarchE Details
The open-label phase III monarchE trial enrolled 5,637 patients (40% premenopausal) with hormone receptor–positive, HER2-negative early breast cancer with clinical and/or pathologic risk factors that rendered them at high risk for relapse. High risk was defined as the presence of four or more lymph nodes, or one to three nodes and at least one of the following: tumor ≥ 5 cm, histologic grade 3, or high proliferation rate (ie, Ki67 ≥ 20%).
After completing their primary treatment (mainly, surgery, endocrine therapy, and chemotherapy) patients were randomly assigned to abemaciclib (150 mg twice daily for up to 2 years) plus physician’s choice of endocrine therapy (5–10 years as clinically indicated) or endocrine therapy alone. The primary objective was invasive disease–free survival.
The addition of abemaciclib to endocrine therapy resulted in an invasive disease–free survival rate of 92.2% at 2 years vs 88.7% with endocrine therapy alone (hazard ratio [HR] = 0.747, P = .0096). The absolute difference was 3.5%, which began to emerge between 9 and 12 months, said Dr. Johnston.
“Beyond 2 years, the data are immature. Obviously, further follow-up will be important to see the ongoing magnitude of this early separation of the curves,” he commented.
Distant recurrence–free survival followed the same pattern, with 2-year rates of 93.6% and 90.3%, respectively (HR = 0.717, P = .0085). The metastases most likely to be prevented were bone (32 vs 81 events, respectively) and liver (29 vs 42 events).
“These high-risk patients, who are at risk of developing early recurrence on their endocrine therapy despite standard-of-care treatment, are now actually having those sites of metastasis prevented through treatment in the early phase of disease with the addition of a CDK4/6 inhibitor,” said Dr. Johnston.
Safety was consistent with the known profile of abemaciclib. The most frequent adverse events were diarrhea, neutropenia, and fatigue in the abemaciclib arm and arthralgia, hot flashes, and fatigue in the control arm. Diarrhea was managed well with antidiarrheal medications and dose adjustments.
Additional Comments
Commenting at the press briefing, Dr. Curigliano said: “The most important thing now is to have data on safety, because most patients have already received chemotherapy and are moving to endocrine therapy. They’ll then receive 2 years of the CDK4/6 inhibitor, so it’s important to know how many patients discontinued treatment due to side effects.”
Dr. Curigliano added that he would like to see a future trial comparing endocrine therapy plus a CDK4/6 inhibitor vs chemotherapy. “We need to understand if there is a special population who can be spared from chemotherapy,” he said.
Disclosure: For full disclosures of the study authors, visit oncologypro.esmo.org.
