I think there’s a lot of data coming out at San Antonio. I think one area that’s particularly interesting is, how do we approach patients who progress on a CDK4/6 inhibitor with endocrine therapy. I think this is an area of huge interest, because we’re not really sure how to best approach these patients. Here we’re going to see data from a lot of different studies that will have, I think, significant impact on what we do...
I think there’s a lot of data coming out at San Antonio. I think one area that’s particularly interesting is, how do we approach patients who progress on a CDK4/6 inhibitor with endocrine therapy. I think this is an area of huge interest, because we’re not really sure how to best approach these patients. Here we’re going to see data from a lot of different studies that will have, I think, significant impact on what we do. One study is the CAPItello-291 trial, which is going to show us data on adding capivasertib, an oral AKT inhibitor to fulvestrant in a patient population who’s progressed on a prior aromatase inhibitor. We already know from the press release that adding capivasertib to fulvestrant did improve progression-free survival in the intent to treat population, but also in the biomarker-driven population. Those patients who have tumors with PI3K, AKT, or PTEN alterations.
This is, I think, really important data to have, because it does lead to a potential option for patients after progressing on a CDK4/6 inhibitor. We’ll also see data from the EMERALD trial where they’ve now done an exploratory analysis looking at how long someone was on their upfront endocrine therapy and CDK4/6 inhibitor and how that correlates with benefit to elacestrant. What you’re seeing is that the patients who had prolonged benefit to upfront endocrine therapy and CDK and had an ESR1 mutation were particularly those patients who experienced prolonged progression-free survival. I think this is really important because when using endocrine monotherapy and someone who’s progressed on a prior CDK4/6 inhibitor, we really do need to figure out who can get away with just endocrine therapy alone. We see a stark drop-off in the curves in EMERALD with a lot of people progressing on first restaging, but then you see a lot of people who have very prolonged benefit who manage to get past that.
These data suggest that maybe those patients who are getting the prolonged benefit are the people with ESR1 mutations and prolonged benefit on upfront CDK4/6. Then I think we’ll also see data from SERENA-2, which looked at the AZ oral SERD camizestrant and compared it to fulvestrant. Again, we know from the press release that this data is also positive. While this is not a registration trial, it does go to suggest that we are going to see a lot more from oral anti-estrogen agents, because we also will see the VeraTech data with ARV-471, which really does show very robust clinical benefit rates around 50% in patients who’ve had prior CDK4/6, and the majority have had prior fulvestrant. I think a lot to come here, and I think it’s going to leave us with a lot of questions about how to appropriately tailor therapy in someone who’s progressed on a CDK4/6 inhibitor.
