medwireNews: Adding abemaciclib to adjuvant endocrine therapy significantly reduces the risk for recurrence in patients with high-risk, hormone receptor-positive, HER2-negative, early breast cancer, show phase 3 trial findings.
“Abemaciclib is the first CDK4/6 inhibitor to show a significant improvement in IDFS [invasive disease-free survival] when combined with endocrine therapy” in this patient population, presenting author Stephen Johnston (The Royal Marsden NHS Foundation Trust, London, UK) told delegates of the ESMO Virtual Congress 2020.
George Sledge Jr speculates on the reasons for the contrasting results of the monarchE and PALLAS trials (5:46)
The monarchE study included 5637 patients with high-risk disease, defined as the presence of at least four positive axillary lymph nodes or 1–3 positive nodes plus one or more of the following features: tumor size of at least 5 cm; histologic grade 3; or centrally evaluated Ki-67 levels of at least 20%.
During a median follow-up of approximately 15.5 months, the addition of abemaciclib, at a dose of 150 mg twice daily for up to 2 years, to standard of care endocrine therapy reduced the risk for invasive disease by a significant 25.3%.
At the 2-year mark, 92.2% of patients who received abemaciclib plus endocrine therapy were free from invasive disease compared with 88.7% of those given endocrine therapy alone, giving an absolute between-group difference of 3.5%.
The findings were similar for relapse-free survival (DRFS), such that the addition of abemaciclib to endocrine therapy was associated with a significant 28.3% decrease in the risk for distant recurrence. And at 2 years, the DRFS rates were 93.6% and 90.3% in the abemaciclib and control groups, respectively, equating to an absolute difference of 3.3%.
Johnston said that “treatment-emergent adverse events [AEs] were very consistent with the known profile of abemaciclib,” with diarrhea the most frequent AE of any grade, occurring in 82% of abemaciclib-treated patients, followed by neutropenia, at 45%.
Certain AEs of interest – namely venous thromboembolism, interstitial lung disease, and febrile neutropenia – were observed more frequently in the abemaciclib than control arm, but “overall the incidence of these events was low,” he pointed out.
A total of 16.6% of patients discontinued abemaciclib due to AEs, while the rate of AE-related discontinuation was just 0.8% in the control group.
Discussing the findings, George Sledge Jr (Stanford University, California, USA) highlighted some key unanswered questions, such as whether the improved DFS will translate into improved overall survival and whether CDK4/6 inhibition can reduce late recurrence.
He also stressed the importance of determining the optimal duration of therapy and developing means to overcome resistance to these agents.
And the discussant concluded: “The decision to use adjuvant CDK4/6 inhibitor therapy is more complex than a simple perusal of IDFS or DRFS data; toxicity (both medical and financial) will need to be weighed against evolving measures of benefit.”
These results were simultaneously published in the Journal of Clinical Oncology.
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ESMO Virtual Congress 2020: 19–21 September
J Clin Oncol 2020; doi:10.1200/JCO.20.02514