Enhancing Breast Cancer Treatment: Expanding CDK4/6 Inhibitor Use in the Early-Stage Setting

Pharmacy Times interviewed Danielle Roman, PharmD, BCOP, manager of clinical pharmacy services and clinical pharmacy specialist, Allegheny Health Network, on her presentation at the Hematology/Oncology Pharmacy Association (HOPA) Annual Conference 2024 in Tampa, Florida titled “Expanding the Use of CDK4/6 Inhibitors to Early-Stage Breast Cancer Treatment.” Roman discusses the efficacy and safety outcomes for CDK4/6 inhibitors in the early-stage setting for breast cancer, as well as key considerations for CDK4/6 inhibitors in this indication.

Pharmacy Times: What was the impetus for expanding the use of CDK4/6 inhibitors, and was early-stage breast cancer the primary indication considered for this expansion?

Danielle Roman, PharmD, BCOP: I think the CDK4/6 inhibitors have had a really important role in breast cancer management in the metastatic setting for many years now. So, we know that they have dramatically improved the activity of treatment regimens. So, I think naturally, when we see such a huge impact in one setting, you want to see does it work elsewhere. So, I think that it was a natural thing to see if maybe there's some activity in the early-stage setting. So, thankfully, we've seen honestly mixed activity. But abemaciclib (Verzenio; Lilly USA, LLC) in particular, has really had some really great improvements in patients that are high risk of early stage breast [cancer].

Pharmacy Times: What have been the efficacy outcomes of expanding the use of CDK4/6 inhibitors in early-stage breast cancer trials so far?

Roman: The efficacy outcomes, when we look at the CDK4/6 inhibitors, we've seen some differing outcomes with trials, we saw that palbociclib (Ibrance; Pfizer) really did not seem to have any benefit in patients in that early-stage setting. Where there has been really exciting information in particular is with abemaciclib in terms of invasive-disease free survival and improving invasive disease-free survival now 5 years out from the 5 years out analysis, and we see that that continues to improve over time. So beyond 2 years on the drug, we're seeing effects continue out 5 years now. So overall survival data is still immature, but definitely great improvements in invasive disease free survival.

A similar story with ribociclib (Kisqali; Novartis), although that data is not as mature yet. So, we're seeing data out 3 years now with improvement in invasive disease free survival, and overall survival is still immature.

Pharmacy Times: What have the trial results shown regarding safety of CDK4/6 inhibitors in treating early-stage breast cancer?

Roman: The safety of CDK4/6 inhibitors in the early stage setting really has mirrored what we have seen in the metastatic setting. So, we certainly know that these agents add toxicity to a regimen, but in general, the toxicities in what we see is manageable. So, I think early identification is appropriate, and patient education is really important with this. And as long as we are aware of this and are appropriately holding or dose reducing supportive care strategies, patients can remain on these treatments and do very well.

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Pharmacy Times: Where are many of these clinical trials in terms of phase, and have any of these trials led to FDA approvals or designations in this indication yet?

Roman: So, I think we've seen some later phase trials here, the phase 3 monarchE trial that was completed did lead to the FDA approval of abemaciclib for 2 years in combination with endocrine therapy for patients who have hormone receptor positive/HER2 negative—but high risk—breast cancer, so they qualify these patients as being lymph node positive. So, either 4 or more positive lymph nodes, or if they had a lower number of lymph nodes, so 1 to 3 positive lymph nodes, they had to have another high risk feature. So really identifying a high-risk patient population there. And so, the FDA approval is within that patient population.

The data with ribociclib is still early, so we don't have an FDA approval from that at this time. But I think we're still waiting for more mature data and certainly could result in an FDA approval in the future.

Pharmacy Times: What are some key considerations for CDK4/6 inhibitors in this indication?

Roman: I think key considerations really go down to patient selection. So, we know that adding toxicity to a regimen with the CDK4/6 inhibitor is inevitable for most patients, so really identifying those patients that are going to benefit vs those patients who may not benefit. So, I think that that's a really important part of this is being able to pick out those appropriate patients to add the drug therapy so that you have the correct balance of benefits and toxicities.