CDK4/6 Inhibitor Toxicity Management

Joyce O’Shaughnessy, MD:One of the things we have to tell our patients when they’re starting CDK4/6 [cyclin-dependent kinases 4 and 6] inhibitors, of course, is about the toxicities and what to expect. And this patient, I would choose letrozole and abemaciclib for her, and I would tell her that diarrhea would likely start as well as potentially some nausea, a little bit of dyspepsia. It might start within a few days and to have loperamide at the ready. Generally, I don’t start the loperamide prophylactically because not everybody has diarrhea, but have it there. If a woman started to have several loose stools, my standard approach is to take 2 loperamide after the first loose stool of the day and then 1 after each subsequent loose stool. And then usually after 1 or 2 doses it will stop.

Now, the diarrhea on the abemaciclib is really the first 4 to 6 weeks. It tends to get much less after that, and what I have found, my patients have taught me, for a woman, they have figured out that eating lighter, not eating heavier meals and eating smaller amounts at a time, blander, will decrease the diarrhea. So women will have, after 4 to 6 weeks, they’ll have 1 or 2 loose stools a week, and it will generally be because of some deviation in their diet. So it’s actually quite manageable over time with the occasional loperamide and some dietary modification.

Other than that, not very much in the way of toxicity, a little bit of fatigue but not very much. In my experience, I’ve probably only had 2 or 3 women where I needed to reduce the dose of abemaciclib because of diarrhea. Most of the women, the diarrhea has drastically decreased over the first few weeks, and they’ve been able to stay at the 150 mg twice a day. But the dose reduction does help, down to 100 mg twice a day. It does help. There’s more diarrhea at the higher dose of 200 mg twice a day, which is the FDA approved dose for the single agent later-line therapy.

Transcript edited for clarity.

Case: A 62-Year-Old Woman WithDe NovoInvasive Ductal Carcinoma

• A 62-year-old woman presented to her gynecologist with a large mass in her right breast
• Breast MRI confirmed the presence of a 6-cm mass and axillary adenopathy
• Labs: ALT 95, AST 70 (elevated)
• Core needle biopsy confirmed ER+ PR (-) HER2(-) carcinoma, grade 3
• CT chest, abdomen, and pelvis showed widely scattered liver metastases