Potential Dosing Strategies to Mitigate CIN

Hope S. Rugo, MD, FASCO: We talked some about the unmet needs in the metastatic and early stage settings and whether being able to effectively prevent neutropenia would change the way you treat your patients. For example, if you give docetaxel-carboplatin every 3 weeks, so patients have to come in less, would you be more likely to give that vs weekly therapy if you were able to more effectively prevent neutropenia and toxicity?

William J. Gradishar, MD: As Rita and Tiffany mentioned, the driver for most of us is finding the most effective regimen. Then we try to support the patient. We’ve already talked at length about the different settings. If you’re in a curative setting, you want to select what you think is going to translate into the best overall outcome and reduce risk of recurrence. If it turns out that a somewhat more toxic regimen achieves that goal, then you have to have ways of attenuating the adverse effect the patient is experiencing. If that’s more profound neutropenia or a greater risk of neutropenia, then we have to focus on how we can succeed at that.

In the metastatic disease setting, we’ve said this many times, the goal is palliation, and we have to focus on quality of life. It’s less about the intensity of therapy, and it could be argued that you may have similar options or outcomes among a number of choices of therapy in that setting, whereas in the early stage setting what we view as the most effective may be a smaller number of regimens.

Hope S. Rugo, MD, FASCO: That’s a good point. Some of the drugs we give cause neutropenia, and we don’t need to prophylax, certainly the CDK4/6inhibitors. Are there other examples where you don’t worry so much about the neutropenia or where we’re giving treatments that cause neutropenia and that’s a problem? Like radiation or other treatments.

I can’t think of many. The use of CDK4/6 inhibitors is interesting because sometimes you’ll see neutropenia even with abemaciclib, which is a pain because you’re supposed to give it continuously, but we have patients who need to go in for their dental work or colonoscopies. That’s the only situation where I see growth factor. Do you take any other approach to it? I recently saw a patient who was getting her labs checked every week and getting growth factors every time she was neutropenic on a CDK4/6 inhibitor.

Tiffany A. Traina, MD: That raises the mechanism of the neutropenia issue, where cytotoxic chemotherapy is destroying those cells and precursors in the bone marrow as opposed to CDK4/6 inhibitors, which I think of as being arrested in time. Those precursors are there, and you need to withhold drug. Understanding the mechanism of the neutropenia helps know how to intervene.

Hope S. Rugo, MD, FASCO: That’s such a good point. Also we learn when you have neutropenia that we see increased risk of infections when you have early progenitor cell damage, which results in normal tissue damages as well the mucosa and various tracks. You don’t really see that with the stomatitis. What we see with CDK4/6 inhibitors is a different mechanism altogether.

Transcript edited for clarity.