Abemaciclib delivers survival benefits to patients with early breast cancer

The combination of adjuvant abemaciclib and endocrine therapy (ET) significantly improves overall survival in patients with HR-positive, HER2-negative, node-positive, high-risk early breast cancer compared with ET alone, the phase III monarchE trial has shown.

Furthermore, treatment with abemaciclib plus ET continues to deliver a sustained invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) benefit at 7 years.

“The survival benefit, together with the substantial reduction in the risk of metastatic disease, represents a favourable efficacy outcome that should be weighed against the short-term known safety profile of 2 years of abemaciclib therapy,” the researchers said. 

The monarchE trial included a total of 5,637 patients, who were randomly allocated to receive either abemaciclib plus ET (n=2,808) or ET alone (n=2,829). Participants received ET for at least 5 years with or without abemaciclib for 2 years.

In the intent-to-treat population, abemaciclib plus ET reduced the risk of death by 15.8 percent, compared with ET (661 deaths; hazard ratio [HR], 0.842, 95 percent confidence interval [CI], 0.722‒0.981; p=0.027), over a median follow-up of 76.2 months. This met the prespecified boundary for significance. [Ann Oncol 2026;37:155-165]

Seven-year OS was 86.8 percent with abemaciclib plus ET vs 85.0 percent with ET alone (absolute difference, 1.8 percent). This survival benefit persisted across prespecified subgroups. Moreover, there were fewer patients living with metastatic disease in the abemaciclib-ET arm than the ET alone arm (6.4 percent vs 9.4 percent).

Notably, participants experienced sustained improvement in IDFS (HR, 0.734, 95 percent CI, 0.657‒0.820) and DRFS (HR, 0.746, 95 percent CI, 0.662‒0.840). At 7 years, IDFS was 77.4 percent with abemaciclib plus ET and 70.9 percent with ET alone (absolute difference, 6.5 percent), while DRFS was 80.0 percent and 77.4 percent (absolute difference, 5.1 percent), respectively.

“The long-term safety data compiled did not support any concerns of delayed toxicities,” according to the researchers.

Long-term benefits

The monarchE study is still ongoing, with continued follow-up to determine the long-term benefits of two additional years of abemaciclib plus ET and its impact on late recurrences and survival.

“Continued follow-up will help define if the reduction in breast cancer mortality with abemaciclib deepens over time, particularly in light of the increasing numerical separation in the OS curves observed at years 5, 6, and 7, with absolute differences of 1.0 percent, 1.3 percent, and 1.8 percent, respectively,” the researchers said.

A substantial difference was noted in the proportion of patients who have experienced distant recurrence and are receiving treatment for metastatic disease, with 33-percent fewer patients in the abemaciclib arm (180 vs 266).

“Given that metastatic disease is incurable, over time this difference in the monarchE trial may lead to a further reduction in breast cancer mortality,” according to the researchers.

“Abemaciclib is the first CDK4/6i to demonstrate the translation of the reduction in the risk of recurrence into a significantly improved OS,” they said. “This marks a major milestone in the development of effective therapies that have the potential to cure more patients with this common form of breast cancer.”