Jacob Kettle, PharmD, BCOP, joins Drs Haumschild and DiMarco in a conversation surrounding findings from the SONIA trial and their impact on shifting mBC treatment strategies.
Ryan Haumschild, PharmD, MS, MBA: I know quality of life is huge. Dr DiMarco, you hit on this earlier, talking about quality of life [being] something we have to evaluate, making sure that patients are having that. I’m going to pose this question to you. How are you evaluating quality of life in your patients, and what effects do CDK4/6s [cyclin-dependent kinase 4 and 6] have on a patient’s quality of life?
Rose DiMarco, PharmD, BCPS, BCOP: That’s a great question. I’ll start with the first one. It is not easy to evaluate quality of life. There are validated tools, there are metrics, there are patient-reported outcomes, or PROs, that we can use. They are complicated. They are sometimes time-consuming, and sometimes they’re not available. As much as I would want to say that I’m giving 30-item questionnaires in clinic to assess quality of life, it’s not happening. I think what is happening, though, is that I know enough about these drugs to know which adverse effects to expect and when to expect them. I ask those questions, and I think that is how pharmacists can measure quality of life. I know the patient when I first met them, I know a patient 6 months later. I know what has changed because I am following up with them at every visit, or I have my learners following up with them with every visit, and I can keep track of that. But from a holistic quality-improvement lens, I think we do need to start to figure out how to get these metrics to be measured appropriately and evaluate it and report it. But there is no kind of standard or consensus way to do that. There was a review looking at all the trials in advanced breast cancer, in the quality-of-life reporting out there. Many limitations with this review; they’re not all using the same model, they’re not all using the same tool. It’s hard to correlate all of that data. But in general, it looks like the CDK4/6 inhibitors don’t worsen quality of life. They might slightly improve or keep it the same. I think that’s what we’re seeing in clinic. I can’t think of many patients who I can honestly say that CDK4/6 inhibitors have made their situation worse. Maybe that’s just because I am so close to them and I am so involved in their care that I’ve been able to manage their adverse effects, so it didn’t impact their quality of life, but I think we’re seeing that across the board. Which you guys agree?
Ryan Haumschild, PharmD, MS, MBA: I think like you said, quality of life isn’t always the clearest to see, but at least incorporating some type of validated scales and at least checking in on it is a great way just to monitor how patients are doing. That’s really important, especially as we see CDK4/6 being positioned more and more. One of the things we’re seeing is, we’re seeing more use and more data out there. Are we going to repeat a CDK4/6 in second line, how do we position it with certain SERDs [selective estrogen receptor degraders] that are starting to emerge within the treatment landscape? And so, Dr Kettle, maybe you can kick us off on this question. I do want to open it up to our panelists as well on this question. How are you positioning CDK4/6 inhibitors in your practice? Has data for the SONIA trial [NCT03425838], where you’re looking at CDK4/6 in both first line and second line and some of the differences there, has that influenced your treatment decisions as a whole?
Jacob K. Kettle, PharmD, BCOP: Great question about the SONIA trial. As we alluded to, the CDK4/6 inhibitors are all 3 of them approved and are supported by the NCCN [National Comprehensive Cancer Network] guidelines both in the frontline metastatic setting—that would be in combination with an aromatase inhibitor—or in the second-line setting with fulvestrant. The SONIA trial asked the question, does it matter where we sequence the introduction of CDK4/6 inhibitors? Frankly, sequencing is one of these big questions out there that we rarely get good data on to support. This is a trial that outlines and gives us some answers. In a nutshell, basically it said it didn’t really matter where we inserted these drugs. Now another looming question is, what about using it throughout the span? Should we use them in front line and switch to a different CDK4/6 in second line? We still don’t have answers to that question yet, but…we’ve tended to lean heavily toward always using these drugs first in frontline settings…. Typically, I agree with this logic; the second-line later-line therapy is never guaranteed. We tend to want to use our best drugs when we get a chance to use them. However, I think the support from this trial gives some credibility. Maybe what someone is going through in their life, dealing with the relapse, maybe a less toxic regimen is better for them at that time. Maybe they’ve got a child who’s getting married. Maybe they’re going through some other [life event], and you all have done such a great job with your clinic experience outlining all the different life experiences that patients also bring to the table. This maybe gives us a little flexibility to say if it makes more sense for the patient, what they’re going through, we don’t necessarily have that strong of a pull to use all our, quote unquote, big guns right out of the gate. Maybe we can save that for later. No, we’re not going to be as compromised in terms of outcome. I really would be curious, especially for our panelists, who spend more time in direct patient care, what your thoughts are on this great question.
Heather Moore, CPP, PharmD, BCOP: [The]SONIA trial was a study that, when presented at ASCO [American Society of Clinical Oncology meeting], brought up a great point, as you mentioned. Do we need to start CDK4/6 inhibition in the first line, or is that something that we could sequence in the second line after progression on endocrine therapy? This was both from a quality-of-life perspective [and] also a financial toxicity perspective. That was another component that was brought up as a secondary end point. What they looked at was time to second progression. What I find to be probably the most significant limitation of the SONIA data is that for patients who were on CDK4/6 inhibitor in the first line, when they progressed, they put them in the second line on monotherapy fulvestrant. When we think about what our current treatment paradigm is, very rarely are we giving monotherapy fulvestrant. We know both based off of the VERONICA [NCT03584009] data and the MAINTAIN [NCT05207709] data that fulvestrant monotherapy in itself may not be the most efficacious. When we think about what we’re typically going to use in the second line, that’s where we’re going to start using next-generation sequencing, that’s when we’re looking for PIK3CA mutation. Can we use alpelisib? Do they have an ESR1 [estrogen receptor 1] mutation? Can we use elacestrant? Some are going more toward therapies that are more targeted toward our patients. Thinking about that, I don’t really think it was a fairer trial design, and I think had we implemented what would be physician’s choice based off of some of those factors in the second line, we may have seen outcomes that were a little bit different than what were presented. It’s something to be taken with a grain of salt. I will say what I take away from the SONIA trial is that, like you mentioned, for patients [for whom] maybe CDK4/6 inhibition in the first line isn’t the best choice, it makes you feel better about making that decision, knowing that you’re still giving them a therapy that is efficacious, that still may have good progression-free survival and thinking about overall survival…. But I think based off what we know from the MONALEESA studies [NCT01958021 and NCT02422615], the MONARCH studies [NCT02107703 and NCT02246621], and thinking about PALOMA [studies] [NCT01942135], that we have enough data to know that it’s probably still best to start with our first-line guideline, recommended therapies.
Transcript is AI-generated and edited for clarity and readability.