Lung Cancer Update, Issue 3, 2016 (Video Program) - Video 5Case discussion: A 56-year-old woman and never smoker with EGFR exon 19-positive, TTF1-positive metastatic adenocarcinoma of the lung
6:44 minutes.
TRANSCRIPTION:
DR MOK: This 56-year-old lady actually presented with a very typical of the right upper lobe mass with multiple pleural nodules. And, certainly, it is adenocarcinoma with TTF1-positive. And then it was exon 19-mutation positive. So, obviously, we put them on first-line TKI. In this case, we gave gefitinib. DR LOVE: And I guess we should say she was a never-smoker. DR MOK: She was a never-smoker. DR LOVE: Just one point, though. In terms of the initial therapy here, I mean, I’m not sure exactly when — how long ago was she treated initially? DR MOK: This was actually almost like 2, 3 years ago. DR LOVE: So now I’m hearing what I — we always like to just go to investigators and say, “What are you doing?” I’m hearing more and more people talk about using afatinib with exon 19 mutations specifically. Are you doing that? DR MOK: Not quite. Now, you’re talking about the overall survival benefit from the combination of LUX-Lung 3 and 6. Yes, it’s an interesting phenomenon to observe in these 2 pooled analyses. But can we change our practice based on pooled analysis of this kind? It’s debatable. Now, look at it this way: The real randomized study is LUX-Lung 7. What if there’s no overall survival benefit from LUX-Lung 7? How are you going to deal with this situation? Because overall survival data will come out any time now. It’s already mature. The data is available. It will be coming out. So if you say the pooled analysis, you say that, “Okay. This is positive.” But then in the real randomized study there’s no overall survival benefit, what are you going to do? So I think there’s still a bit of cloudiness in it. And that’s fine. For this reason, I think yes, you can consider it as use, but I would not reserve it entirely for exon 19 mutations. DR LOVE: When I looked at this case, I said, “Not only is this a poster child case for lung cancer, this is a poster child case for oncology today nowadays,” which is, first of all, she goes down the usual path. She has a great response to the gefitinib for 14 months. DR MOK: Right. DR LOVE: How did she tolerate it, incidentally? DR MOK: Perfect. I mean, living a normal life. DR LOVE: No skin problems? DR MOK: Some skin problem, but it’s very manageable. A lot of these patients just got a bit of paronychia. And so really, a lot of these patients live a very normal life for a duration of time. DR LOVE: But then, unfortunately, 14 months, she has disease progression. She has now a pleural effusion, cytology-positive. And was this in the cytology fluid that you got the T790M mutation? DR MOK: Actually, these days there are 2 ways of looking into it. And you can either do it in the plasma or you can do it in the tissue. In her case, it’s actually from the cytology sample we can do it. DR LOVE: Really? That makes sense. DR MOK: But then using the plasma test, we got, actually, about 70% to 80% of sensitivity. DR LOVE: You mentioned plasma and then tumor. Then the other thing I just heard about in the last few days was urine. DR MOK: Urine is feasible, but actually if you have pleural effusion, the effusion is actually even better. DR LOVE: Yes. Oh, absolutely. But the thing that kind of struck me is a rociletinib study. But I thought I saw that they had patients in there — I think there were 4 patients whose tissue was T790M-negative and urine was positive, and they responded. DR MOK: Definitely. I think that is the one from the urine. But then the better data is actually going to come out from the AURA studies. DR LOVE: The serum. DR MOK: The serum. DR LOVE: Yes, of course. DR MOK: Yes. And — because the AURA study, there’s only 1 data set that you have tissue, plasma, as well as the response to osimertinib. DR LOVE: But the thing that I had heard was something about there aren’t DNases in the urine. So sometimes you can have a positive urine and negative serum and tissue. Is that right? DR MOK: I think you can do that. But, on the other hand, a lot of this is by chance. I mean, you’re talking about fragments of DNA swimming around. Whether you going to catch it or not, it’s never going to be 100% concordance. So I won’t say urine’s better than the plasma or plasma better than urine. I think it’s assessable. Whether you can catch it or not, I doubt if you will ever have anything close to 90% or 100% sensitivity. It’s probably going to stay around 80% or so. And so to me, plasma is easier to handle than the urine. DR LOVE: Maybe, but, I mean, I guess the bottom line is, there are a lot of patients where it’s not that easy to get tissue. I mean, they’ve got bone mets. They have tissue that’s tough to access. You had a pleural effusion there, but sometimes that’s kind of difficult. It seems like any — so is the thinking that if you see a mutation, whether it’s serum, urine or whatever, you’re done, you’ve got it? But if you don’t, you’ve got to keep going? DR MOK: Absolutely. So if you are plasma- or urine-positive, the specificity is about 90%. Plasma sensitivity is not that high. So even if it’s negative, then you have to go to the tissue biopsy. DR LOVE: So the reason I say this is really a poster child for oncology is, okay. You find out she’s got a T790M mutation. This must have been maybe a year or so ago, I’m going to guess. DR MOK: Yes. DR LOVE: But you knew what you wanted to do, but the drug wasn’t approved yet, which is, you wanted to give her osimertinib. DR MOK: Exactly. So I gave her chemotherapy, because I knew that eventually I’d get the osimertinib, because I’ve been involved with the program. DR LOVE: I mean, everybody saw the data. We knew it was going to have to come out, but — DR MOK: Exactly. DR LOVE: — it’s just amazing that she was in this window when it wasn’t available, so you gave her chemo. DR MOK: I just kept her going. And then she responded well. The effusion disappeared, and gave her maintenance, and then she continued to do well. DR LOVE: So she had carbo/pem? DR MOK: Pemetrexed/carbo. DR LOVE: And then pem maintenance? DR MOK: Yes, pem maintenance. DR LOVE: Wow! So how long was she on that? DR MOK: She was stable for 4 more cycles after maintenance, probably a total of about 8, 9 months. And after that, then her CA starts to rise again. So this indicated that she was not going to do so well. And so by the time the “Name the Patient” program’s available, I applied for it. And she got the drug, and she’s fantastic right now. DR LOVE: So yes, I say being an oncologist nowadays is, you wake up in the morning. You check your phone. You see what’s been approved. And then you try to figure out what you’re going to do about it. DR MOK: That is the excitement of this time. DR LOVE: Anyhow, so this lady makes it through to the approval of osimertinib, gets osimertinib. What happened once she got on it? DR MOK: She responded. And then CA — risk, so-called, dropped very nicely, and the effusion’s under control. And she continues to do well. DR LOVE: Any tolerability issues? DR MOK: In her case, no. I mean, so far my experience with osimertinib has been quite favorable. There’s the occasional patient with the platelets going down a little bit. And there are occasional patients with hepatic toxicity. But overall, it’s quite well tolerated. |