Start low to stay long: adapted dose escalation as a patient-centered strategy for adjuvant Abemaciclib
Year: 2026
Type: article
Abstract: The treatment landscape of early hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer has changed substantially over the past decade.For many years, adjuvant endocrine therapy represented the central systemic backbone after completion of local therapy and, when indicated, chemotherapy.Recently, the integration of cyclin-dependent kinases 4 and 6 (CDK4/6) inhibition into the adjuvant setting has introduced a new therapeutic principle: targeted escalation beyond endocrine therapy for patients at increased risk of recurrence (1).Abemaciclib, administered for two years in combination with endocrine therapy, has demonstrated sustained improvements in invasive disease-free survival and overall survival in patients with high-risk, node-positive disease (2).However, the clinical success of any adjuvant therapy depends not only on its biological effectiveness, but especially on the therapy adherence.Adjuvant therapy is reducing the risk of recurrence, so the expected benefit is probabilistic, delayed and cannot be "seen" by the patients.On the other hand, adverse events are immediate, tangible, and sometimes disruptive.Thus, a treatment that is highly effective in a trial may fail to achieve its intended real-world benefit if patients are unable or unwilling to continue it.In this context, tolerability is not a secondary convenience; it is a prerequisite for efficacy.Particularly in light of retrospective real-world data suggesting that dose reductions of CDK4/6 inhibitors may not compromise survival outcomes (3,4).The ToleRability of Abemaciclib Dose Escalation (TRADE) study by Mayer and colleagues addresses precisely this clinically relevant interface between efficacy and deliverability (5).The investigators inverted the classical approach of starting with the maximal dose and reduction in case of side effects.A gradual treatment approach was designed to reduce the risk of early intolerance instead of waiting to manage side effects once they appear.The study evaluated a simple dose-escalation strategy: abemaciclib was initiated at 50 mg twice daily for two weeks, increased to 100 mg twice daily for another two weeks, and then escalated to the standard 150 mg twice-daily dose if clinically appropriate.Dose escalation required the absence of ongoing grade 3-4 https://tbcr.amegroups.
Author: Stefan Lukac
Institution: University Hospital Ulm
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7223089514