Case 2: Choosing a CDK4/6 Inhibitor in ER+ Breast Cancer

Tiffany Traina, MD: This patient is a, presumably, postmenopausal woman who is presenting now with metastatic breast cancer that is poorly differentiated, ER positive and HER2 negative with visceral metastases.

I think we have consistently seen from multiple clinical trials that incorporating 1 of the 3 CDK4/6 [cyclin-dependent kinases 4 and 6] inhibitors to a backbone endocrine therapy of either an aromatase inhibitor or fulvestrant has profoundly impacted improvement for our patients, in terms of progression-free survival.

My treatment paradigm often will include a first-line aromatase inhibitor and CDK4/6 inhibitor. My choice of CDK4/6 inhibitor is largely driven by differentiation by toxicity. Of the 3 inhibitors available, I generally will think about palbociclib as associated with myelosuppression. Monitoring generally requires CBC [complete blood count] every other week for the first couple of cycles.

All of these agents have a warning about potential pneumonitis that we have to be aware of. That’s how I mentally associate the toxicity profile with palbociclib.

For ribociclib, this is an agent where the monitoring is a little bit different. We do need to keep an eye on not only CBCs but also liver function studies. We need to be cognizant of the potential for drug-drug interactions leading to QTc [corrected QT interval] prolongation, and so monitoring of EKGs [electrocardiograms] is also a concern.

Reviewing drugs and other medications for potential drug interactions is also needed, and LFT [liver function test] monitoring.

And then the last agent for consideration is abemaciclib, and this agent tends to have a little bit less in the way of the myelosuppression. But it is associated with a bit more in the way of diarrhea. And so I think although we do not have a head-to-head comparison in terms of efficacy of all of these drugs, they do appear to have somewhat comparable hazard ratios in their trials and perhaps pretty comparable magnitude of benefit of treatment.

Where I see them really differentiating themselves is driven by the varying toxicity profiles.

I think the CDK4/6 inhibitors differentiate themselves from one another largely based on toxicity profiling. These agents do have differences in their dosing schedule, whether it’s intermittent or continuous, or twice-a-day or once-a-day dosing.

In terms of toxicity, they all seem to have some degree of myelosuppression. Palbociclib is relatively well tolerated. I think about myelosuppression as one of its main adverse effects, although not much in the way of neutropenic fever, per se.

There is a potential warning about pneumonitis with these drugs, as a class. When we look at ribociclib we do need a slightly different monitoring schedule, in addition to looking at blood counts and concern for cytopenias. We need to monitor liver function studies. We need EKG monitoring for the potential of QTc prolongation, and there may also be a greater tendency for drug-drug interactions. This requires a slightly different monitoring schedule.

I think the last agent, abemaciclib, has a bit less in the way of myelosuppression, but it does have higher degrees of diarrhea and GI [gastrointestinal] toxicity. A potential differentiator is also CNS [central nervous system] penetration with abemaciclib, and so these characteristics tend to, perhaps, influence choice of one over another.

But I do think that efficacy is comparable across the board.

Transcript edited for clarity.