Ryan Haumschild, PharmD, MS, MBA: I appreciated the discussion about therapy because it’s important that we think about real-world evidence. If we go from an aromatase inhibitor to fulvestrant, what is the clinical benefit? Speaking of clinical benefit, perhaps Dr. Dent can lead the way on this. What are some of the clinical endpoints that you consider therapy goals? Often when I talk to patients, they may be more interested in overall survival. Some [are more interested in] progression-free survival. What are those endpoints that stand out to you that you use to monitor response to therapy? At what point do you consider switching patients if you feel they are not meeting that desired endpoint?
Susan Faye Dent, MD, FRCPC, FICQS: That is a good question. When you look at drug approval, overall survival has historically been the gold standard. Everyone wants to live longer with their illness. They want to survive. As a clinician, I think patients still benefit from progression-free survival, which is what many of the studies look at. All of the CDK4/6 inhibitors we have available were originally approved on a progression-free survival basis. Because if you can prevent someone from advancing longer, that means you’ll keep them well for longer. It is important that you also keep them away from chemotherapy longer.
On the backbone of that, some studies have reported time to onset of chemotherapy as an endpoint, which is interesting. Quality of life is an important end point. All those things are looking at how to keep someone on therapy that is best tolerated, works, and has the least impact on quality of life [are important]† Overall survival is important, but other endpoints, such as progression-free survival, time to chemotherapy and quality of life, are equally important.
Ryan Haumschild, PharmD, MS, MBA: When we talk about some of these clinical endpoints, we recognize that we can’t get there alone. It [requires] involve the patient. Good adherence to treatment, management and understanding of treatment goals are important. Pharmacists play an important role in that, so I’m going to put this question to Dr. Moore, who works directly in the clinic with breast cancer patients every day. From your perspective, what is the important role that pharmacists play in treating these patients and sometimes in screening, training, monitoring and following up on the diagnosis for mutations? Give us a little context about the important role you play as a pharmacist in the clinic.
Heather N. Moore, PharmD, BCOP, CPP: First, we are the drug experts. That’s essentially what we do. Like dr. Dent said, the common drugs prescribed and approved by the FDA in oncology are changing so quickly that there are many complexities and toxicities that open the door for pharmacists. You mentioned a few. One of them is education. [It’s important to] make sure the patient feels empowered with the therapy he is taking and how he is taking it at home. There are many things that we overlook, including whether it is taken with food. This is important from the patient’s perspective.
I think of toxicity management when we think of all of our therapies within the breast cancer setting. I cannot emphasize this enough. We’ll get into this a bit more, but I’m thinking specifically of alpelisib-induced toxicities, hyperglycemia, rashes, neutropenias, diarrhea, and nausea that we see with some of our CDK4/6 inhibitors. Although we are moving away from chemotherapy, there are so many toxicities associated with many of our targeted therapies that we need to know how to deal with them. What good is a drug if you can’t stay on it?
The other important aspect for pharmacists is drug interactions. We think of drug interactions, and most people think of CYPs, not just from a pharmacokinetic standpoint, but also from pharmacodynamic interactions. A lot of what we see are patients with comorbidities. Many of our patients are post-transplant patients, patients who may have chronic kidney disease, or patients with multiple co-morbidities, where we essentially need to find ways to make the drug fit the patient. We basically find the best therapy for patients and help identify which different drugs within a class might be best. Probably the best example of this would be with CDK4/6 inhibitors. We have 3 different [drugs] within that class, and [we need to] choose what is best for this patient.
Susan Faye Dent, MD, FRCPC, FICQS: Can I build on that? I want to make a clear plea for a pharmacist on board. I’m lucky that we work side by side in the clinic and how valuable that is. More importantly, you asked me another aspect of the previous question that I didn’t quite get around to, which was, what would make you change your therapy? Why would you change therapy in a patient taking something for metastatic disease? There are clearly 2 things. Does it work? You want to make sure that their disease does not progress and that it is at least stable. Ideally, it can shrink.
Second, and most importantly, do they tolerate it? We cannot overestimate its importance. Over the course of my career, I’ve introduced therapies to the clinic and we say, “It looks great on paper. It’s a statistically significant impact on care, and it’s clinically significant,” but the patient cannot tolerate it. Why? Because we have not adequately addressed the adverse effects and toxicity of that treatment. I’m a big believer in not only looking at whether that treatment is effective for the patient, but how we can be proactive in monitoring and preventing the toxicities associated with that treatment. That’s where working with a pharmacist is very important.
Transcription edited for clarity.