Lung Cancer Update, Issue 3, 2016 (Video Program) - Video 4T790M mutation testing and treatment of metastatic nonsquamous NSCLC after disease progression
3:19 minutes.
TRANSCRIPTION:
DR LOVE: If you have a patient who starts out on an EGFR TKI, afatinib or erlotinib, usually in this country, responds and then has disease progression, first of all, how do you approach the issue of testing for T790M? Do you get serum? Do you get tissue? Urine? DR BLUMENSCHEIN: So I do serum and tissue. And again, because the serum comes back a little sooner and I’ve identified a number of patients that way who had T790M. And in general, if there’s diffuse progression, T790M-positive, we’ll transition from their first-generation EGFR tyrosine kinase inhibitor over to osimertinib and they’ll take that. There’s tumor heterogeneity. And so I’ve had patients who had 1 spot that grew and everything else was controlled, and these were patients who’d been on erlotinib for some years. And we biopsied that particular patient, and sure enough, it was a T790M mutation in that particular area that was growing, but all the other sites of disease, which were numerous, were controlled. So we ended up irradiating that 1 spot, and then we’re holding osimertinib on the back burner in the event the other sites of disease become resistant. DR LOVE: Interesting. You said you did serum and tissue. What about urine? Again, Heather Wakelee at ASCO presented just a few cases, but it looked pretty interesting. DR BLUMENSCHEIN: It did look interesting. But no, that’s not a common practice for us. DR LOVE: And in terms of T790M-negative patients, which I guess is around half or less of those patients, what are the options you think through? DR BLUMENSCHEIN: So it depends on if we find something that’s targetable. Do they have MET alteration that we can proceed with? Yes. Is there something else? It’s roughly 60% that are T790M and in that other 40% it could MET. That’s one that comes to mind. Other mutations can occur. But if they don’t’ have something that we have a drug for or a clinical trial for, then I think it’s appropriate at that point to initiate chemotherapy if they haven’t had chemotherapy yet, immunotherapy. It depends on where they are in their treatment cycle. DR LOVE: But again, if all they’ve had was 1 TKI, now they have disease progression, would they be more likely to get chemo or a checkpoint inhibitor? DR BLUMENSCHEIN: If they’ve had 1 TKI and have disease progression, I’m inclined to give them chemotherapy and then utilize the checkpoint inhibitor later. DR LOVE: I’ve heard people talk about looking at PD-1 levels in that situation, people who don’t look at it up front in the typical situation. What about that thinking? And in general, are you looking at PD-1 levels at all in your decision-making? DR BLUMENSCHEIN: So we’re starting to do that. And when you asked me that question, I was assuming that we would be testing for that as well as a part of it. Clearly if someone’s a high overexpresser for PD-L1, then it makes sense to give them an inhibitor of PD-L1 or PD-1 inhibitor. But I still think, even those patients who are PD-L1-negative, clearly looking at the Phase III data, they do, at least, in terms of single-agent chemotherapy, have equivalent outcomes and less toxicity. So I think it’s a reasonable thing to do in that population. In the refractory setting, I’m not routinely testing. In the front-line setting, we’re starting to test. |