Preferred Treatment for ALK-Rearranged NSCLC


Experts have a discussion about their preferred treatment approach for newly diagnosed ALK-rearranged non–small cell lung cancer (NSCLC).

Benjamin Levy, MD: I’ll just go around here. If you could give me your take on first. Is everyone an alectinib prescriber in the first line? Are there potential patients that you would use something else like brigatinib or lorlatinib? Alex, I’ll let you start.

Alex Spira, MD, PhD, FACP: I’m a brigatinib only because we did ALTA-1L, so old habits die hard, right? There’s no other reason than that right now. That’s pretty much it. When people ask me, I usually tell them either one.

Benjamin Levy, MD: Either one. You’re more of a brigatinib doc than an alectinib doc?

Alex Spira, MD, PhD, FACP: Again, I’m more of a brigatinib, again just because we did the study here. As I said, same as you, creatures of habit.

Benjamin Levy, MD: Got it. Jacob?

Jacob Sands, MD: I’m more alectinib. Alectinib is just so well tolerated on top of everything and it’s just easy to use. For me that’s part of it as well.

Benjamin Levy, MD: Melissa?

Melissa Johnson, MD: I also pull alectinib first. I’ll say that the CROWN data made me reconsider decision because patients did so well on lorlatinib, but I tend to save that as my second-line choice.

Benjamin Levy, MD:I guess Ed already brought this question up as well. What do we do next? A patient is on alectinib and do we do biopsies upon progression? Does it make sense? I’ll give you 2 counter arguments. One is, yes, patients who are on alectinib who develop a G12O2R are sensitive to lorlatinib, high response rates. Patients without a G12O2R have a response rate to lorlatinib similar to chemotherapy. Does it even make sense to do a liquid biopsy or a tissue biopsy? Melissa, I’ll let you start again. What do you do in this setting? How do you use the information, or do you interrogate the tissue for subsequent treatment decisions?

Melissa Johnson, MD: I will admit that plasma testing is my favorite, particularly in a sequential way, mostly because it’s easy. The tissue is absolutely the gold standard and I don’t want anyone to hear me say that I don’t do that, especially when I have a vexing case where I’m not quite sure what the next step is. I absolutely use plasma when patients progress, but it is an academic exercise currently. I do it so that I’m not caught off guard. We are seeing more emergence of MET in patients posttreatment with alectinib and other TKIs [tyrosine kinase inhibitor]. And there you would do something different, right? You would try to add capmatinib potentially to it, doing that right now. It’s important to look and we’re not quite sure what we’re going to find yet.

Benjamin Levy, MD: Jacob, your everyday practice, what you’re doing post alectinib?

Jacob Sands, MD: I agree, I would test and see what you find but generally speaking, lorlatinib can be used pending other kinds of alterations like Melissa pointed out. But it’s important to test. I test. Anyone on targeted therapies I tend to test at the time of progression.

Benjamin Levy, MD: Liquid, tissue, or both?

Jacob Sands, MD: Blood first because it is so easy and then depending on the scenario and depending on what’s in there, then I definitely would consider biopsy if further testing is needed. If there’s something in there, if it’s negative but something pops up that you can entrust it’s true negative, then I don’t necessarily go to tissue, but if there’s not much showing up and there’s clear progression, it also kind of depends on the scenario. If there’s clear progression and liquid is not showing anything, then getting a biopsy makes sense. If there’s some progression but it’s not rapid and the liquid’s not showing a lot, then I might still follow a little bit. It just kind of depends on the pace of things as well as far as how quickly I pull the trigger on getting a biopsy.

Benjamin Levy, MD: Great. Ed, what do you do every day for patients post-alectinib?

Edward Kim, MD, MBA: Post-alectinib, I’m still a traditionalist. I do like the fact that there are liquid biopsies out there, but I still try to get tissue and we can usually expedite that quickly within a week. We worry mostly about the payment. We want to make sure that these tests are covered if you have serial NGS [next-generation sequencing] testing done, but I always start with that. We used to gather the blood at the same time, so that it could be defaulted in case we had an insufficient quantity. But I like to look at that and then see if it’s one of those resistant mutations. If that’s the case I’m happy. If not then we’ve just got to go to chemotherapy.

Benjamin Levy, MD: And your chemotherapy is generally carbo/pem, pem [carboplatin, pembrolizumab] alone, carbo/pem/bev [carboplatin, pembrolizumab, bevacizumab]?

Edward Kim, MD, MBA: Yes, it’s usually carbo/pem. I don’t necessarily use the IMpower150 sort of regimen.

Benjamin Levy, MD:Okay. Alex, final thoughts. Brigatinib or alectinib for you. What do you next?

Alex Spira, MD, PhD, FACP: Pretty much on par. I will say in the patients I’ve seen progression, it’s never one of these. It’s one of these super slow. I don’t know if I’m just different than others. Obviously, there’s a selection bias. But I always look at these patients and they’ve grown a few millimeters and you’re wondering can you get that biopsy and then the same thing with the NGS in the blood. Is there going to be enough DNA shedding and you’re really going to get a good sample and is a negative test really going to be accurate? I struggle with that a lot. I will say I’m not a huge fan of lorlatinib. I know there’s a big debate in the frontline setting and I don’t use it, as you heard, from the frontline of the debate. But in the second-line setting I try not to use it mainly because I don’t want to become a cholesterol manager and I’ve had some people with some really crazy psychological things. One person just became out of mind almost on it for a little while. I didn’t even realize because she wasn’t my patient first until the husband came in and said, you know, she’s completely different. I had no idea. I just thought it was her behavior. But I do what everybody else does.

Benjamin Levy, MD: I would agree. Lorlatinib, we give quite a bit of it post-alectinib but I would agree that following cholesterols is important and the CNS [central nervous system] cognitive issues are there, that the neuropsychiatric stuff has to be watched closely when these patients are on it. Melissa?

Melissa Johnson, MD: I’m curious if you think about adding chemotherapy to the lorlatinib.

Benjamin Levy, MD: I generally don’t add chemotherapy to lorlatinib. I usually use it as; lorlatinib generally is my go-to. Looking at the data again from the second line in the lorlatinib trial, it seems like the response rates outside of those that did not have a G12O2R were roughly the same as they were with chemotherapy cross-trial comparisons. Both are acceptable. I don’t know if Alex, if you wanted to answer as well.

Alex Spira, MD, PhD, FACP: No. I don’t add chemotherapy either.


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