For patients with prior HR+HER2- localized breast cancer currently receiving adjuvant endocrine therapy, is there a time period in which you would no longer recommend adding adjuvant abemaciclib?

This is a great question and I hope we eventually have data to guide us. I also do not know how insurers will handle these types of requests. This high-risk ER+ population has a 10-year risk of distant recurrence between 20 to 40% with continued risk of recurrence over 20 years based on the EBCTCG data (Pan et al., PMID 29117498). Some recent preclinical data demonstrated that among the 3 CDK4/6 inhibitors, abemaciclib was the most potent inducer of cancer cell death through inhibition of lysosome function. (Hino et al., PMID 32304130) Also, abemaciclib can cause permanent senescence and apoptosis of sensitive cancer cells due to prolonged cell cycle arrest. (Torres-Guzmán et al., PMID 29050219) If the longer term follow up data from Monarc...

The benefit of adjuvant abemaciclib shown in the monarchE trial was in fact, recently updated (Johnston et al., PMID 41110697) and is showing a sustained reduction in recurrence risk (HR 0.664) compared to HR 0.75 in the initial analysis.

However, the question of delayed therapy and whether the impact would be the same as seen in up front (within protocol-specified 12 weeks after the last non-endocrine therapy – e.g. chemotherapy or surgery or radiation) versus a longer delay, for example, 6 or even 12 months is unanswered. I personally would feel comfortable using abemaciclib in a case where a clear benefit is projected up to a year (or maybe even more) after the completion of non-endocrine therapy. This is based on the fact that delayed en...

There is no prospective data on using it over 2 years. I am comfortable recommending it for up to 2 years.