Mark Enyedy: So let me start with the market question. And you can talk about PICCOLO and CCN. So in terms of discretionary use of this product outside the label, the first thing to keep in mind is that our label is platinum-resistant ovarian cancer in patients who’ve received 1 to 3 prior lines of therapy who are FR alpha positive. So — what we observed very early on was that consistent with the NCCN guidelines that physicians were using the product in later line patients. So beyond a patient who had 3 prior therapies, and that continues as we speak. We then observed that there are patients who might not be — might not qualify as FR alpha high who nonetheless are getting therapy as monotherapy, where the FR alpha expression is close to what would be considered FR alpha high.
Just as a reminder to folks, FR alpha high is defined as 75% of the patient’s tumor sample expressing FR alpha at 2-plus intensity staining. And so when a pathology report comes back from our labs, it has 2 readouts. One is positive or negative based on whether it meets that cut point of 2-plus intensity staining. But also, there’s a numerical score with respect to the expression level. So it’s stated in 5 percentage point increments, so 75, 80, 85, up to 100 and then downwards for 70, 65 and so on. What we hear anecdotally through market research in our advisory boards is that many physicians with a 70% reading will initiate monotherapy. As the FR alpha expression levels go down, there’s the opportunity to engage around combination use. And again, the NCCN guidelines are supportive here where they include use of the product for patients with medium and low levels of expression.
And so we — as I said, we see use in later lines. It’s a little hard to — we can’t sort of match a patient who had a 70% level of expression with monotherapy use at this point, the data — we’re not able to from a data perspective to match those 2 things. And then we do see an increasing use of combination and it comes through most prominently in our market research relative to the claims data, which lag a little bit. And I think a number of you on the call have produced your own sort of market research studies that show both existing and anticipated increasing use of combination therapy. I don’t know if you want to add anything to that?
Isabel Kalofonos: Yes. I just want to say awareness of NCCN guidelines has increased, and it has been included in some of the pathways to some of the centers. And NCCN guidelines has silence around high medium or low monotherapy in addition to lifting the value of the combination. So in addition to being used in later lines of therapy, yes, we see use on mediums and lows, particularly in combination.
Michael Vasconcelles: And this is Mike. With respect to your second, third and fourth questions. Let me make a point about this patient population that perhaps haven’t been quite explicit about. But when a patient with natural history, who has still platinum-sensitive disease in third or subsequent lines, there’s an important dichotomization around the relative platinum sensitivity that a clinician is thinking about when they think about appropriate therapy at this stage. And that’s important as we think about the full data when we see those data next year because the durability of response, just like the objective response rate are going to be influenced whether the patient population has a platinum-free interval that’s relatively short versus a platinum-free interval that’s relatively long.
