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ASCO has published a follow-up to its on adjuvant CDK4/6 therapy for early breast cancer. The companion article focuses on questions clinicians may face as they implement the updated recommendations.

The take-home points from the companion article, published in , are as follows, the authors said:

• When deciding whether or not to recommend a CDK4/6 inhibitor, the absolute risk of recurrence should be considered, using all available information. We prefer adjuvant CDK4/6 inhibition for patients at the highest risk, we would consider therapy for patients at intermediate risk, and would not offer CDK4/6 therapy for patients at the lowest risk.

• Among patients who would have been eligible for both the monarchE and NATALEE trials, we currently prefer abemaciclib over ribociclib, given the longer follow-up and shorter duration of treatment. Patient preference and potential side effects should also be considered.

In the following interview, companion article co-author Rachel Freedman, MD, MPH, of Dana-Farber Cancer Institute in Boston, who also co-authored the guideline update, discussed some of the key considerations and decision-making factors in more detail.

How did the patients included in monarchE and NATALEE differ, and how did that influence your recommendations?

Freedman: There is overlap between the two clinical trials in who was eligible. However, there are some differences as well. Both trials targeted people with breast cancer who were at "higher risk" for recurrence, but the trials defined this in different ways. There are nuances, but in general, the NATALEE trial allowed patients with stage 2 cancers who didn't have node involvement, while monarchE required lymph node involvement plus other features if there was limited node involvement.

Basically, NATALEE included a broader, lower-risk population than monarchE. Both trials did not include patients with stage I cancers but did include those with stage III cancers.

Accurately estimating risk is crucial when considering adjuvant CDK4/6 therapy, but available tools are imperfect. What are some of the prognostic variables and patient characteristics that a given tool may not take into account?

Freedman: We use a lot of factors every day in the clinic. We have to balance the risk of one's recurrence from their cancer and the side effects of a treatment that may lower that risk.

The higher the risk for recurrence, the more we want to do, but this has to be put into context with the person's preferences, underlying medical conditions, and the degree of anticipated benefit of any treatment we give. This is true of any treatment we use in breast cancer, not just CDK 4/6 inhibitors.

As you mentioned, shared decision-making is key as individual patients will weigh the benefits, risks, and burdens differently. Can you give an example from your practice of a patient whose personal preferences influenced the decision in an unexpected way?

Freedman: I have had patients who have significant underlying health conditions that are of more concern to them than their breast cancer, and they worry about the side effects. If I feel the benefits are still important to consider, I will sometimes offer a trial of therapy, with the idea that we can make changes if side effects occur that aren't manageable. Often, with dose modification or medication changes, we can make things better.

When choosing between abemaciclib and ribociclib, how is the choice of endocrine therapy relevant?

Freedman: The NATALEE trial did not include patients taking tamoxifen, but only those taking aromatase inhibitors (AIs) because of previous concerns about the safety of the tamoxifen-based combination. The monarchE trial allowed any adjuvant hormonal therapy -- tamoxifen or AIs.

When using these agents, I try to stick to the treatment regimens tested in the trials. It is of note that tamoxifen with abemaciclib resulted in higher thrombosis risk than when abemaciclib was paired with AIs in monarchE, so I tend to avoid that combination in many cases unless the AI isn't tolerated.

Is there anything else you want to make sure oncologists understand about these recommendations?

Freedman: I think these data all need to still mature, and I look forward to seeing how things evolve with regard to recurrence and survival over time. This will all help inform decisions further.

Read the companion article to the guideline update here and expert commentary about it here.