medwireNews: The 4-year results from monarchE indicate that the invasive disease-free survival (IDFS) gain offered by adjuvant abemaciclib in people with high-risk, hormone receptor-positive, HER2-negative, early breast cancer is maintained even after the 2-year treatment period.
Indeed, the benefit of adding abemaciclib to adjuvant endocrine therapy (ET) “deepened in magnitude” over time for both IDFS and distant relapse-free survival (DRFS), the presenting author Stephen Johnston (The Royal Marsden Hospital, London, UK) told delegates of the 2022 San Antonio Breast Cancer Symposium in Texas, USA.
These data “further support” the adjuvant use of abemaciclib in this patient population, he added.
The randomized phase 3 trial comprised 5637 patients with hormone receptor-positive, HER2-negative, node-positive disease who were considered at high risk for recurrence based on clinical pathologic features or Ki-67. Participants either did or did not receive abemaciclib 150 mg twice daily for up to 2 years alongside standard of care ET with an aromatase inhibitor or tamoxifen.
In the current analysis, conducted at a median follow-up of 42 months, the Kaplan–Meier curves continued to separate, such that the 4-year IDFS rates were 85.8% for patients who received abemaciclib plus ET and 79.4% for those given ET alone. This equated to an absolute benefit in favor of the CDK4/6 inhibitor of 6.4 percentage points, which was greater than that seen at the 2- and 3-year timepoints, at 2.8 and 4.8 percentage points, respectively.
Similarly, the 4-year DRFS rates were 88.4% and 82.5% in the abemaciclib plus ET and ET alone groups, respectively, giving an absolute difference favoring abemaciclib of 5.9 percentage points, which was greater than the difference of 2.5 percentage points at 2 years and 4.1 percentage points at 3 years.
Johnston also presented a post-hoc analysis that estimated yearly piecewise hazard ratios (HRs) for IDFS and DRFS, which showed that “the magnitude of the abemaciclib benefit increases year on year beyond completion of the study treatment period, suggesting a potential carry-over effect.”
Specifically, the piecewise HR for an invasive disease event or death decreased from 0.782 in year 0–1 to 0.618 in year 2–3, decreasing further to 0.602 at years 3 and more, while the corresponding HRs for a distant relapse event or death were 0.725, 0.651, and 0.581.
The presenter noted that the overall survival data remain immature at this interim analysis, but there was a numerical difference between the abemaciclib and control arms, at 157 deaths versus 173, at data cutoff, and “follow-up is ongoing.”
Johnston told delegates that “the safety data in the trial were consistent with previous analyses and no new safety signals were identified.”
And he continued: “The majority of adverse events occur early in patients on-study and are managed by appropriate dose holds and dose reductions, which were permitted in the study to allow patients to stay on-study for the 2-year treatment period.”
These findings were simultaneously published in The Lancet Oncology.
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