Real-World Data on CDK4/6 Inhibitors in HR+/HER2- Metastatic Breast Cancer and Ongoing Trials

Transcript:

Komal Jhaveri, MD, FACP: Talking about real-world data, how do we think about real-world data? How do you think about wanting real-world evidence? How does that supplement you in your thought process when you’re managing your patients in clinical trials?

Gregory Vidal, MD, PhD: Real-world data is really helpful for me. It’s only really confirmatory from what we see in clinical trials because clinical trials are very sterile, very prescribed. Sometimes those patients don’t really represent what we see in clinic and real-world data suggesting that the evidence is the same, the benefit is the same, [or] the toxicity is sort of the same. We have some of that, that we’ve had in some of the trials looking at really large data sets for real world. So the activity we see for CDK4/6 over AI [aromatase inhibitors] is still maintained. The POLARIS trial [NCT03280303 ], I think, looked at sort of a quality of life that is still maintained. So that’s very, very helpful for me when I’m thinking about my patients, that I’m actually giving them a drug that might slightly be different in a different setting from the clinical trial. [It] might be an older patient [who] might have a little bit more comorbidities, but the data is maintained. So it’s very helpful.

Komal Jhaveri, MD, FACP: So it’s supplementary, it’s complementary.

Gregory Vidal, MD, PhD: Yes. Complementary.

Komal Jhaveri, MD, FACP: It helps you expand the label to a patient that in fact potentially would have not been eligible for the trial.

Gregory Vidal, MD, PhD: Exactly.

Komal Jhaveri, MD, FACP: It gives you that comfort. I’ll probably make that a little more difficult then and put an extra question there. So VK was telling us about how palbociclib is not something that we use. We have negative trials. We now have real-world data supporting the overall survival benefit that has been seen with palbociclib. How does that help now that you have a prospective trial that hasn’t necessarily shown that other prospective trials for ribociclib and abemaciclib, MONARCH-3 [NCT02246621] interim analysis? How did this real-world dataset then help with that?

Aditya Bardia, MD, MPH: I think the real-world data provides confidence. If I have to switch from ribociclib to palbociclib or if there’s already a patient on palbociclib, I can continue that. So it’s supplementary. Real-world data will never have the same level of evidence as a randomized trial.

Komal Jhaveri, MD, FACP: It’s good to have a complementary reason. It supports many things in clinic but doesn’t replace level 1 evidence for approval. Very well said. Any other advances in the first-line setting with other novel agents that we should be keeping an eye out for? Aditya, did you see something that might impact changes in the first line?

Aditya Bardia, MD, MPH: I think there’s a lot of interest in oral SERDs [selective estrogen receptor degraders] and there are a couple of ongoing trials looking at oral SERDs; elacestrant as first-line therapy in combination with the CDK4/6 inhibitor. Now, those trials are using palbociclib as the CDK4/6 inhibitor. In the future, we would want to see other inhibitors as well. There’s also a trial called SERENA-6 [NCT04964934], which is kind of a hybrid first/second line, more like 1.5 [lines], trial, which is looking at patients who get AI plus a CDK4/6 inhibitor [in the] first line and monitoring for ESR1 mutations. If there are detectable ESR1 mutations at that time, making a switch to continued AI [or] a switch to a SERD, elacestrant. So that’ll be an interesting trial to see if we should monitor patients and then based on their tumor biology and evolution switch therapies.

Komal Jhaveri, MD, FACP: Thank you. I think that will be exciting to see if PARSIFAL [NCT02491983] was a negative study when we tried to look at fulvestrant vs AI…we could not show superiority for that in a phase 2 study. Now these are phase 3 trials with an oral SERD, and we will have to see if somehow they delay the emergence of ESR1 [mutations] as in SERENA-4 [NCT04711252], or we switch with SERENA-6 with emergence of ESR1 mutations, would we make a difference? I think we saw the updated results from the PADA-1 study [NCT03079011] as well. I think one thing that we are all realizing is in PADA-1, certainly there was benefit to that switch adaptive strategy without radiological progression. Will this translate into overall survival benefit, or will it just make us utilize these therapies a little sooner based on what we’re learning from these newer technologies? I don’t think PADA-1 is necessarily suitable for addressing that question definitively, given the sample size there. The design was not powered to necessarily look at overall survival, but something along those lines is [what] we need to know just so that we understand the true merit of such an approach that we’ve been trying to incorporate into our clinical trials. Certainly, [it’s] a very novel scientific question and we’re excited to see that.

Gregory Vidal, MD, PhD: The other thing about PADA-1 is how feasible it is to be doing these serial biopsies in that patient population? Well, serial CT, liquid biopsies ctDNA [circulating tumor DNA] and following it, we have difficulty getting one in those patient populations. Getting numerous and multiple over time, looking for it, may be a difficult proposition.

Transcript edited for clarity.

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