Abemaciclib becomes the first agent of its kind approved for the adjuvant treatment of early breast cancer


Stephen Johnston, MD, PhD, provides an overview of the effect of the approved CDK4 / 6 inhibitor abemaciclib on patients with early-onset breast cancer and how it will advance investigative efforts in this space.

Abemaciclib, a CDK4 / 6 inhibitor, has been approved in combination with tamoxifen or an aromatase inhibitor for the adjuvant treatment of adult patients with early breast cancer with hormone receptor positive, HER2-negative and node at high risk for recurrence and a Ki -67 score of at least 20%, as determined by an FDA-approved test, based on data from the Phase 3 MonarchE trial (NCT03155997).

The 36 month invasive disease free survival rate in patients treated with abemaciclib plus tamoxifen or an aromatase inhibitor (n = 1017) was 86.1% (95% CI, 82.8% -88.8 %) versus 79% (95% CI, 75.3% -82.3%) in patients treated with tamoxifen or an aromatase inhibitor alone (n = 986). Approximately 16% of patients in the control group experienced an event versus 10.2% in the experimental arm (HR 0.0626; 95% CI: 0.488-0.803; P = 0.0042).

In an interview with OncLive®, Stephen Johnston, MD, PhD, head of medical oncology and head of the breast unit at the Royal Marsden NHS Foundation Trust and the Institute of Cancer Research in London, England, gave an overview of the effect the approval of the CDK4 / 6 inhibitor for patients with early-onset breast cancer and how this will advance investigative efforts in this space.

What was the clinical rationale for studying this combination in this patient population?

In the MonarchE trial, we examined patients deemed to be at high risk for recurrence after a diagnosis of [hormone receptor–] HER2-negative early breast cancer. We specifically selected those who had positive lymph node disease. We know they are more at risk. Layers of risk on top of that [baseline] were treated as [either] 4 or more [positive] nodes, or if they had 1 to 3 [positive] lymph nodes. [Also,] the patients had additional risks, such as a large tumor, high grade, or high proliferation. Despite the best level of care, we estimated that this population would, on average, be [experience] relapse at a rate of 20-30% in the first 3-5 years, so there was room for improvement.

CDK inhibitors have already been shown to add [benefit] to endocrine therapy in advanced disease, as they overcome endocrine resistance and control cancer longer. The question was: In early breast cancer, could we select a population at risk and show that the addition of [a CDK inhibitor] for 2 years in addition to their hormone therapy would be [reduce the rate of] early recurrence in the first 2 to 3 years?

Please explain how this approval will affect the landscape of early breast cancer treatment.

It is the first inhibitor of CDK4 / 6 [approved] in early breast cancer, and this is based on the level of efficacy observed in the MonarchE trial. The FDA label specifically added the high Ki-67 group, which had around 2,500 patients in the trial, as they had an even higher risk of recurrence if they had an increase [number of positive] lymph nodes and other risk factors. It is a group which obtained a very significant gain in survival without recurrence at 3 years.

This is a particularly high-risk group, where [the FDA] believes that early recurrences in the first few years could potentially be avoided by adding the CDK inhibitor. [The approval] represents a very important milestone in early hormone-positive breast cancer.

[With the approval,] we now have a new endocrine treatment, which we do not have [seen an] accreditation for nearly 20 years. It’s a paradigm shift because the last new treatment was aromatase inhibitors in 2002. It represents our progress in understanding primary endocrine resistance, [identifying] patients who are doomed to relapse despite the best therapies and the development of interventions to stop these early relapses.

This is a very important step for the small group of patients with high risk disease, for whom hormone therapy [alone] will not be the solution. We can make a significant difference for them. For many patients, hormone therapy alone and their current treatments can cure them. But, for about 15% of all patients with [hormone receptor–]positive breast cancer, they are doomed to relapse relatively early despite endocrine treatment. For this group of patients, whom we believe we can now identify, this significantly improves their results.

What future for abemaciclib in combination with endocrine therapy?

There are about 6 or 7 ongoing studies with CDK inhibitors in early breast cancer, looking to see if we can further narrow down the group of patients who benefit. The trials in a neoadjuvant and adjuvant setting are [evaluating CDK inhibitors] face to face chemotherapy because chemotherapy is not always the answer for luminal hormone positive breast cancer. This will be important because you may be able to avoid the toxicity of chemotherapy with this effective combination if it can be as effective or better.

Other studies aim to refine the selection of resistant endocrine diseases. [Investigators are using a] technique of very short-term exposure to hormonal treatment in the 2 or 3 weeks preceding the surgery and measurement of Ki-67 [expression] to see if the hormone treatment stops this. If so, hormone therapy alone can be very effective. However, hormone therapy will not stop cell proliferation in about 20% of patients. [To overcome this,] POETIC-A study investigators [NCT04584853] identify those where proliferation is not disabled and randomize them to abemaciclib [or endocrine therapy] after [surgery].

The label [indicates abemaciclib] for large ganglion tumors. the [patients in POETIC-A] may have smaller tumors or disease without lymph node involvement, [representative of] a group of patients with tumors that are biologically resistant to hormone therapy, who may not have high clinical pathological risk factors. This may be the next parameter where this drug could be refined to play a niche role.


  1. Verzenio. Prescribing information. Eli Lilly and company; 2021. Accessed November 5, 2021. bit.ly/3BUraOU


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