The Advent of Oral Oncolytics and Patient Access

Joyce O’Shaughnessy, MD: Hello, and thank you for joining this video editorial series titled, “Advances and Best Practices in the Utilization of Novel Agents in Metastatic Breast Cancer.” Oral oncolytics account for 25% to 35% of the oncology pipeline. When treating metastatic breast cancer patients, oral CDK4/6 [cyclin-dependent kinases 4 and 6] inhibitors offer patients another option, a very important option, in their breast cancer treatment. Today we’re going to explore the clinical and patient benefits of CDK4/6 inhibitors, the multidisciplinary approach in treating patients, and overall best practices for the use of oral oncolytics, specifically the CDK4/6 inhibitors.

I’m Dr Joyce O’Shaughnessy. I’m the chair of breast cancer research at Baylor University Medical Center, Texas Oncology, and US Oncology in Dallas, Texas.

Today I’m joined by Michael Reff, a pharmacist and executive director of the National Community Oncology Dispensing Association in Cazenovia, New York.

Later in the series you’ll also hear from Dr Sara Tolaney, assistant professor of medicine at Harvard Medical School and attending physician of medical oncology at the Dana-Farber Cancer Institute in Boston, Massachusetts; and Lindsay Shaw, a nurse practitioner at Dana-Farber Cancer Institute in Boston as well. And you’ll hear from Dr Kate Jeffers, an ambulatory oncology clinical specialist at University Colorado Health in Colorado Springs, Colorado.

Thank you so much for joining us, let’s begin.

It’s helpful to kind of put it into a real-life context—the oral CDK4/6 inhibitors, which have become the No. 1 go-to in the metastatic setting for ER [estrogen receptor]-positive metastatic breast cancer. Patients are on them for a long time, too. We have 3 available. We have palbociclib, ribociclib, and abemaciclib. All of them show very big improvements in progression-free survival, doubling the amount of time in the first-line setting that patients are on these agents compared to endocrine therapy alone. So, of course they’re combined with aromatase inhibitors. In the second-line setting, they’re combined with fulvestrant.

Just recently at ESMO [European Society for Medical Oncology], and then published in the New England Journal of Medicine, it was shown that when fulvestrant is combined with palbociclib for patients who had used a prior aromatase inhibitor and didn’t have highly-refractory disease—like they blew through endocrine therapy, got some benefit from it, and then they went on to fulvestrant plus palbociclib— there was a survival advantage seen with the CDK4/6 inhibitor. So in a phase III setting, that’s really the first survival advantage that we’ve seen. This was not in the overall treated population; it was in the sensitive population. But most patients fell into that category. Only about 20% of patients were really refractory. So it just shows you the emerging importance of these agents.

Michael Reff, RPh, MBA: Sure.

Joyce O’Shaughnessy, MD: But they have toxicities. Most importantly, we’ve got to be monitoring the complete blood counts with the neutropenia of palbociclib and ribociclib. In a fair percentage of patients, that does lead to the need for dose reductions. Deciding how to integrate that while avoiding the waste of having somebody receive their next month’s supply only to realize that it is the wrong dose is a big issue.

Michael Reff, RPh, MBA: Sure.

Joyce O’Shaughnessy, MD: On that note, how does that work in terms of the dosing and the specialty pharmacy versus in-house pharmacy, for example?

Michael Reff, RPh, MBA: That’s a great question and a great lead-in. Our patients are fortunate that they have 3 options in a space that is relatively new—within the last 4 years or so. This innovation has allowed us and allowed patients to help and maybe even bridge into the next therapy that hasn’t been discovered yet. That’s what I think the CDK4/6 inhibitors have really done for our patients and our practices.

But you talked about some of the issues with dosing and toxicities, and the efficacy profiles of these compounds. They’re relatively similar, in most respects, but they do have some nuances that we are well aware of. I think it helps the clinicians know, when they have discussions with patients, which product to select. And then in the medically integrated dispensing or the medically integrated pharmacy team, we have conversations with the prescribers—whether it’s yourself, as an oncologist, or an advanced practice professional. This helps us decide on a course of therapy or a treatment regimen. The medically integrated team can also help look within the EMR [electronic medical record].

That’s the benefit of having that in-house continuity of care a practice can provide, whereas a specialty pharmacy may not have the expertise or infrastructure because they don’t have the electronic medical records that we do at our practice. We utilize the electronic medical records to the fullest extent possible to provide additional value to the patients and the whole care team. We can interact with prescribers on what may be the best choice, not only on the selection but also as maintenance. You mentioned dose reductions. How do we manage that? We work in coordinated efforts with our medically integrated team.

Joyce O’Shaughnessy, MD: Yes. I’m always calling my pharmacist saying, “OK, is a proton pump inhibitor OK here? Remind me of the food.” Palbociclib, for example, should be taken after food, but that’s not the case with ribociclib and abemaciclib. As I recall, it’s OK to take a proton pump inhibitor, but I always have to call and double check on that. And obviously if someone has had a history of some marrow that’s been a bit on the sensitive side, then we’ve got to be careful with using CDK4/6 inhibitors because they really cause myelosuppression. Maybe you want to start at a lower dose, for example. And then we have to think about monitoring the patient, how to time the next dose, and decide what dose you’re going to give next, before you know what the counts are going to be, etcetera.

Michael Reff, RPh, MBA: I think that’s a great example of where the pharmacy team or the medically integrated team can help, whether it’s the pharmacist within the pharmacy itself or the oral oncology nurse navigator who is taking a look at if the patient is coming in on schedule to see how they’re doing, right? If there is a refill on a prescription, maybe it’s not necessary because the patient hasn’t followed up on the treatment schedule that the prescriber wanted them to. And by utilizing that EMR and fully taking advantage of the information, and then by communicating back to the prescribers when they have that interaction that we can have because we are medically integrated… The patient is in front of us, or the patient is on the phone. We know who they are intimately. We are now communicating back to the prescribers on information that we gain or glean from our patients.

Joyce O’Shaughnessy, MD: You know, you just brought up something that I have known for a long time in practice. Some lives have been lost in the curative setting because we didn’t have systems in place to see who wasn’t coming back or who wasn’t filling those scripts. If they don’t take their endocrine therapy, we know that their outcomes will be worse. And the CDK4/6 inhibitors, before long, will be in the adjuvant curative setting. Even now in the metastatic setting, they’re not going to get the benefit if they’re not filling the scripts, or if they’re not coming back and getting them renewed. We haven’t had that kind of infrastructure in practice to be able to really make that happen for patients.