Kelly McCann, MD, University of California, Los Angeles, shares insights on the results from the phase 2 TRADE study. This prospective, single-arm study aimed to assess whether a dose-escalation strategy of adjuvant abemaciclib improved drug tolerability among patients with early-stage HR-positive, HER2-negative breast cancer.

According to study authors, “Use of an adjuvant abeam[ciclib] dose escalation strategy allowed a greater number of [patients] to reach and maintain the 150 mg dose at 12 [weeks] than in monarchE.”

These data were first presented by Erica Mayer, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

Transcript:

Hi, I am Kelly McCann. I'm a breast medical oncologist at UCLA.

Right now for our patients with hormone receptor-positive, HER2-negative breast cancer who are stage 3, or if they have 1 to 3 lymph nodes and have either a 5 cm tumor or a grade 3 tumor, they're eligible to have abemaciclib in the adjuvant setting That's given as 2 years of abemaciclib in addition to an aromatase inhibitor, plus or minus ovarian function suppression for 5 years, ideally.

One of the aspects of abemaciclib that sometimes leads to patients discontinuing therapy is that they can develop GI toxicities, namely diarrhea. It does tend to get better with time, but one strategy that many of us had been using and that was addressed by this trial was attempting to do a dose escalation strategy to try to ameliorate the diarrhea. For example, when we've had neratinib in the past, we learned that giving this medication, neratinib, which causes diarrhea can be ameliorated by going from a low dose up to a higher dose. Abemaciclib is not necessarily the easiest one to do that with because the pills only come in 50 mg, 100 mg, 150 mg packs, whereas neratinib starts with taking 6 pills at the maximum dose, and so you can start low and go up.

In the TRADE study, patients were given 50 mg of abemaciclib for 2 weeks, followed by 100 mg for 2 weeks, and then up to 150 mg from there on out. When patients on this trial were given a dose escalation strategy, they tend to have less diarrhea and more patients were able to continue therapy. 

That said, it is not the worst thing in the world to have a patient get all the way up to 150 mg BID, have diarrhea and need to dose reduce. We know that abemaciclib works at lower doses, and so it's important to tell patients upfront that just because they're not at the dose that was the highest studied in the clinical trials, that doesn't mean that they're not getting efficacy. It’s important to be with your patient and discuss this ahead of time with them so that they don't feel like they are not getting the efficacy that they want from that treatment.

One of the questions that came up during the session was that, right now there's no blister pack or any way to do this strategy unless we prescribe the 50 mg dose and then do more of the neratinib type strategy where we start with just a pill pack of 50 mg and then go up by that strategy. Because otherwise, there is a concern that if we are prescribing the 50 mg, the 100 mg and then the 150 mg, that patients are going to have delays in treatment.

Source:

Mayer E, Trapani D, Kim S, et al. The TRADE study: A phase 2 trial to assess the tolerability of abemaciclib dose escalation in early-stage HR+/HER2- breast cancer. Presented at the 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract #517