Common Adverse Events With CDK4/6 Inhibitors

EP: 1.Introduction: A 54-Year-Old Woman With ER+/PR+ Breast Cancer

EP: 2.Adjuvant Therapy Options for HR+ Breast Cancer

EP: 3.CDK4/6 Inhibitor Breast Cancer Clinical Trials

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EP: 4.Common Adverse Events With CDK4/6 Inhibitors

EP: 5.Case Patient Prognosis

EP: 6.ER+ Early Breast Cancer Future Directions and A Note on Ki-67 Analyses

Lowell Hart, MD, FACP: The adverse events for the CDK[4/6] inhibitors were found on the clinical trials to be very similar to what we’ve known for several years in using these drugs in patients with advanced breast cancer.

With all of them, there can be some suppression of the bone marrow. I mentioned that 1 of the things that when I talk to patients, I tell that these drugs can sort of put your cancer to sleep temporarily and that they can do the same thing on other growing cells, including growing cells in the bone marrow.

With ribociclib [Kisqali] and palbo [palbociclib; Ibrance], as I mentioned before, you need to take a week off so each 4 weeks. Even with abemaciclib [Verzenio], you can get some suppression of the bone marrow and you can see some neutropenia and anemia, although it’s usually not severe enough, in most cases, that you need to have those reductions. But those were seen in some of the patients on the trial.

The 1 side effect that you can see more with abemaciclib than with the other drugs is diarrhea. We commonly do see some diarrhea early on in both patients with advanced disease and now that we’re using it in women with early-stage breast cancer.

I always tell the patients to be prepared for this and to expect it. It’s seen in probably about two-thirds of the patients. There’s some degree of diarrhea. It’s rarely a grade 4 diarrhea that you need to make a major dose reduction or whole doses and that sort of thing.

That will happen in sort of 10% to 15% of patients, but if you treat the diarrhea aggressively with use of drugs like loperamide as soon as it’s seen, I always tell patients to be sure to have that loperamide around the house and have it available so that they can start taking it when they see some diarrhea.

The other nice thing about using abemaciclib in the setting, and in the advanced disease setting too, is that the diarrhea does not continue at the same frequency throughout the entire period, which can be 2 years of the patient’s treatment.

It usually does decrease, and the data’s been that the diarrhea is mostly seen in those first few weeks, the first month or 2 that the patient is taking the drug and then it usually gets much better after that.

I found in using the drug as an adjuvant, these patients are very motivated. Oftentimes they have already completed chemotherapy. There can be some diarrhea seen with a docetaxel [Taxotere] regimen, too.

We see a little bit of diarrhea with that so they’ve had some experience dealing with these sort of things, and they’re very motivated and understand the data, that this drug isn’t—they’re not going to be taking it for the rest of their lives and it will improve their chance of remaining free of cancer.

With proper monitoring and with proper rapid response to any diarrhea or other symptoms that come up, the large majority of patients can stay on treatment. There are other less common side effects that can show up.

You can have increases in liver function tests with any of the CDK4/6 inhibitors, so those are things that need to be watched for. At the start, it’s important to check the patient’s blood counts and when they come in to get their blood counts checked, we check their chemistry too, to make sure those things are OK and just have to follow the package inserts.

Compared to other drugs that we use, I don’t think that the side effect profile is extremely difficult to manage with any of the CDK4/6 inhibitors. Now that we’ve used them for the last 5 years or more in many, many women with advanced breast cancer, I think, and more in the adjuvant setting, [it] is not especially difficult for most experienced oncologists.

This transcript has been edited for clarity.

Case: A 54-Year-Old Woman with ER+/PR+ Breast Cancer

Initial Presentation

• A 54-year-old, postmenopausal woman presents with a newly diagnosed lump in her right breast
• She has no family history of cancer and underwent menopause at age 50

Clinical work-up

• Imaging demonstrated a 2.4-cm solid mass in the right upper quadrant with no suspicious lymphadenopathy identified
• Core biopsy: positive for invasive ductal carcinoma, ER 100%, PR 97%; HER2 1+ and FISH negative; Ki-67 45%; modified Bloom-Richardson grade 3
• Lumpectomy and sentinel lymph node biopsy performed
  • Tumor size is 2.4 cm, and 3 LNs are positive for metastatic disease
• 21-gene assay recurrence score is 30
• pT2N1M0, stage IIB
• ECOG PS is 0

Treatment

• Patient underwent partial mastectomy with no residual disease
• She is given radiation therapy to intact breast
• She is started on adjuvant chemotherapy with cyclophosphamide and docetaxel

Followed by adjuvant therapy with AI + 2 years of abemaciclib