New Biological Insights and Recent Therapeutic Advances in the Management of Lung Cancer: A Clinical Investigator Think Tank
A 35-year-old woman in respiratory failure due to lung cancer who needs rapid initiation of treatment
9:04 minutes.
TRANSCRIPTION:
DR LANGER: So this is a 35-year-old Japanese-American woman, a never smoker, presented to an outside hospital with rapidly progressive left-sided chest pain, shortness of breath on exertion back in December of 2013. She was found to be hypoxic, with a pulse ox of 74% on room air, which improved with facemask, ultimately about 93%. She was transferred from this outside institution to our ICU, ultimately weaned to 6 liters, and the scans showed a very large, left lower lobe mass, with diffuse circumferential pleural thickening. There was a small to moderate left pleural effusion as well as incidental bilateral pulmonary emboli. She was started on low molecular weight heparin. Pleural fluid cytology came back positive for adenocarcinoma. And we performed a core biopsy of the left lower lobe mass, which again confirmed adeno. It was also TTF1-positive. So the question that we had here, particularly in such a young woman, otherwise reasonably healthy, at least prior to this diagnosis, should we wait for molecular testing — female, Asian ethnicity, never smoker, adenocarcinoma — or start chemotherapy empirically? She’s super sick, and time is of the essence. And again, given the circumstances, what markers do you ask for, and what would be the acceptable timeline to getting these results? Do you just restrict it to EGFR and ALK, since those are the two that are actionable, or do you go for a more extensive panel? And so do you really have the time to wait? So Mark, you’re one of the leading experts on this. DR LOVE: What happened to her at Memorial, Mark? DR KRIS: So you have a critical decision as to how much time you have before initiating therapy. And based on the way you presented the case, there really isn’t much time. We try to fix everything fixable, so you fix the PE. We might go after the effusion. DR LANGER: We did. DR KRIS: And that, too, would add some breathing room. So one thing I learned from the IPASS trial is that, if you don’t have a mutation, you’re not helping the patient at all. And in the IPASS trial everybody was the same characteristics of the patient you talked about, but if you didn’t have the mutation, the stuff just didn’t help. And people actually did worse. So I don’t think empiric treatment is recommended. And if I felt pushed to do something, I would give chemo. So different institutions, though, for their full molecular profile, have different timelines for it. And they’re generally too long for a patient like this. I think everybody’s in agreement with that. DR LOVE: How long would it take to get an ALK and EGFR at your place? DR KRIS: It depends on the quality of the specimen hitting the lab. It’s a little tougher in a case like this, where you’re making a diagnosis at the same time. So the flow of the pathology department, some of the tissue and thinking goes down the diagnostic side first. They don’t immediately just take that specimen and send it off to molecular. So what our pathologists have done now to try to make this happen — or in a good way, is, they do immunohistochemistry testing, and they routinely do it for ALK and for the common EGFR mutations. And that’s what would be done. And based on that, we can usually get that back in 48 hours. DR LANGER: Oh, wow! Okay. DR KRIS: Yes. It’s like doing TTF1 or CK7 or whatever. They’re in the working CLIA lab, and, actually, when they report the diagnostic stuff now, our pathologists report this. So we have those 3 things. And if we didn’t have any of those 3 things, we would go and give chemo. DR LANGER: Do you have to order it explicitly, or they know? DR KRIS: We don’t. It’s done reflexively on a specimen that’s lung cancer. DR LOVE: So at your place, Corey, how long would it have taken to get you her — DR LANGER: It took 5 days. DR LOVE: Five days. DR LANGER: So it took an extra 2 to 3 days, but we were very explicit. The second biopsy was done with the intention of proving both lung cancer and obtaining molecular markers. DR LOVE: So you did another biopsy to get more tissue? DR LANGER: The first was just a cytology. We knew it was adenocarcinoma. I mean, radiographically it looked like a thoracic cancer. So we impressed upon the pathologists the necessity of knowing EGFR and ALK quickly, and they did it about as quickly as they could, which was not quite as quick as Memorial but certainly much quicker than if we had sent it for a full panel. DR LOVE: What did it show? DR LANGER: EGFR was negative. She was ALK-positive. DR CARBONE: Just a comment that in someone who’s in an intensive care unit, is critically ill with adenocarcinoma, it’s not entirely clear that chemotherapy is a good thing in that setting. Historically, PS2+ patients don’t benefit from chemotherapy. And I think it can complicate things, especially in a critically ill person with neutropenia, infection, all the other problems. And the key will be getting fast turnaround on the molecular testing. DR LANGER: Because of her clinical characteristics and our high suspicion that she would have some actionable molecular marker, we deliberately tried to hold off on systemic chemotherapy. And she was improving between the anticoagulation and a PleurX® catheter and appropriate oxygen support and antibiotics, so her performance status went from 4 to maybe two and a half. But we felt we at least had the luxury of waiting several days before empirically starting on chemo. DR CARBONE: But the pushback I would have for Mark is, our pathologists are reluctant to report out immunohistochemistry for EGFR/ALK and then have us act on that as a nonapproved biomarker for the drug. DR OXNARD: We’re doing ROS also, actually, in our pathology lab. DR CARBONE: No, I understand. The first step. Do you confirm it with FISH or with the FDA-approved test before you act on that? DR OXNARD: Sometimes you can’t wait. You should confirm it, but when the suspicion is high, I think you can act on it and wait for the confirmatory FISH to tell you if you made the right decision afterward. DR LOVE: Does everyone agree that they would not treat empirically, for example, a targeted therapy without a test? Anybody here who would do that? What would you say, Jeff, in terms of the likelihood, statistically, that this lady was EGFR-positive, ALK-positive or other? DR OXNARD: In a young patient with this kind of aggressive presentation, this is consistent with ALK. We have a number of experiences of these people getting crizotinib, coming off the vent sometimes, dramatic responses. And I think ALK can have a very aggressive phenotype. And we have definitely had discussions at our tumor boards for patients like this, saying, “We can’t get the answer. Maybe we should just start crizotinib and give it a try. Your question is appropriate. It is still not our standard, and Mark is right. If they don’t have the genotype, they won’t respond. And you might make the wrong decision. Sometimes it presses your hand. And I think this question will keep coming up as we learn about these phenotypes and how they present. DR LOVE: I never heard this thing about ALK being more aggressive. DR OXNARD: We see it a lot. They get blood clots. Often they show up with blood clots, I see. And I’ve also often seen them to be very aggressive in their presentation. DR TSAO: So I actually would probably disagree, Jeff. I mean, you’ve got an Asian female, never smoker. I mean, we see these. And EGFR mutation can be very aggressive. So this actually is — also, they’re hypercoagulable. So this is a very common presentation for an EGFR mutant. So if I had to make that call in this case, I’m like David. We are not really going to treat unless we have the actual FDA-approved assay. So we wouldn’t have used IHC. Our turnaround time is probably within 2 weeks to get a tissue genotype back. And so I actually may have considered giving erlotinib to this patient in an ICU on a vent, because I wouldn’t have treated with chemo, for the risk of infection. DR KRIS: Yes. The first thing, I think David makes a very important point about the chemo, that we do not recommend chemo for somebody who is bedbound. Again, I was hoping that between treating the PE and the effusion that we could get her up and around. The question about the IHC test, we just decided that this woman had lung cancer based on the pathologist looking at those slides and maybe doing a TTF1. What’s the FDA approval for that? I mean, we just made perhaps the most critical decision in this woman’s care based on the expert opinion of a pathologist. And all these other issues are, to me, tangential. |