CDK4/6 Inhibitors for Advanced HR+ Breast Cancer


An overview of CDK4/6 inhibitors available for patients with advanced or metastatic HR-positive breast cancer, and recommendations for managing common adverse events associated with therapy.

Kevin Kalinsky, MD, MS: So there’s palbociclib [Ibrance], ribociclib [Kisqali], and abemaciclib. All 3 are approved in patients with hormone receptor-positive, HER2-negative disease along with endocrine therapy.

The mechanism of action is similar across the agents. The palbociclib and ribociclib are given 3 weeks on and 1 week off. Abemaciclib is given twice a day continuously. Their safety profile is a little bit different.

Palbociclib and ribociclib causes more neutropenia. The rates of febrile neutropenia are so low, about 1.5%. But we see that the rate of neutropenia is lower with abemaciclib compared to the other 2.

However, abemaciclib has a different toxicity profile, and we see gastrointestinal issues or some diarrhea particularly early on.

The other thing with ribociclib, just to be mindful of, is that at week 1 and week 3, and then also at week 5, it’s important to do EKGs [electrocardiogram] just looking for QT prolongation [when the heart muscle takes a longer time to contract and relax than usual], and there can be some drug-drug interactions just to be mindful of.

The most common adverse event that we see with palbociclib and ribociclib can be neutropenia. So it is important to check that blood count every 2 weeks for the first 2 months.

And then, I generally, because I’m seeing patients in the metastatic setting monthly, continue to check that blood level. For abemaciclib, the main toxicity that we can see can be gastrointestinal issues. And even when you prescribe that medication, it comes with Imodium. So it’s important to have that on hand. If diarrhea develops, you don’t need to take that medication prophylactically. But if it develops, and generally patients tend to tolerate that agent once you get through a month or 2, that’s when we see the highest rate of diarrhea. And of course, we can manage these with dose modifications.

Other potential side effects include things like fatigue, and there is a slightly higher rate for alopecia. And then when you compare utilizing abemaciclib in the early stage versus the metastatic setting, what I would say is that really it’s important for these first few months to stay in close contact with the patient, just is in terms of gastrointestinal issues.

And the early-stage setting, we’re not seeing those patients ultimately as frequently as we do in the metastatic setting. So once a patient’s been on abemaciclib, and they seem to be tolerating the medication, and they’re several months in, we’re seeing these patients a little less frequently than what we do in the metastatic setting.

If new symptoms occur, then of course, we’ll see the patient, but that seems to be the big differential in terms of how we manage early versus metastatic disease.

Transcript edited for clarity.

Case: A 67-Year-Old Woman with ER+/PR+ Breast Cancer

Initial Presentation

  • A 67-year-old, postmenopausal woman presents with a newly diagnosed lump in her left breast
  • She has 2 grown children, no family history of cancer, and underwent menopause at age 48
  • PMH is significant for hypertension that is well controlled with medication

Clinical work-up

  • Imaging demonstrated a 4.4-cm solid mass in the right upper quadrant with no suspicious adenopathy
  • Core biopsy: positive for invasive ductal carcinoma, ER 100%/PR 40%; HER2 IHC 1+; Ki-67 30%; modified Bloom-Richardson grade 3
  • Lumpectomy and sentinel lymph node biopsy performed
  • Tumor size is 4.5 cm, and 2/5 LNs are positive for metastatic disease
  • 21-gene recurrence assay score is 30
  • T2N1M0, stage IIA
  • ECOG PS is 0


  • Patient underwent partial mastectomy with no residual disease
  • She is started on adjuvant chemotherapy with cyclophosphamide and docetaxel
  • She is given radiation therapy to intact breast
  • Followed by aromatase inhibitor + 2 years of abemaciclib
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