Treating Newly Diagnosed ALK+ NSCLC



H. Jack West, MD: Let’s turn to ALK-positive patients. We’ve gotten more and more data and some more options. At this point, would you say that alectinib is the clear first-line standard of care for a newly diagnosed patient?

Charu Aggarwal, MD, MH: I would say yes, I think for the same arguments, or similar arguments that we made for osimertinib for the EGFR-mutant lung cancer patients, the survival advantage plus the CNS [central nervous system] activity that we see with alectinib is far superior to, at least, crizotinib. I mean, that was the trial comparison, and that’s certainly, in terms of tolerability, my first choice.

Hossein Borghaei, DO: I agree. I think alectinib has been my standard of care, and I guess the only question is: Should brigatinib also be considered as a potential frontline option at this point?

H. Jack West, MD: At this point, ceritinib has an approval. I don’t think we spent a lot of time agonizing over its place, but brigatinib has positive data from the ALTA-1L trial against crizotinib, but it’s early data; and we have an alternative in alectinib that is a pretty well-tolerated and very efficacious agent. So where does brigatinib or even ceritinib bubble up here?

Hossein Borghaei, DO: That’s a good question. I don’t know, exactly. Ceritinib—probably further down the line for somebody who is progressing. At this point, I’m still starting with alectinib as my standard of care, or as my first choice. I think the data that I’ve seen with brigatinib are very thought-provoking, but again, we don’t have a head-to-head comparison of brigatinib versus alectinib in this patient population, and we’re unlikely to get anything like that. So I think then you look and see what the activity of the other agents are, post alectinib, and try to select a drug that best suits that, if you just use clinical parameters.

This concept of doing mutational analysis after each progression on one of these TKIs [tyrosine kinase inhibitors] has been percolating. It’s only possible in a few centers. It takes time and all of that, but I think it’s an interesting approach because, again, talk about personalizing the delivery of care. You start with 1 drug, you do a biopsy, you figure out what the mutation in that tumor is, and you offer a corresponding drug that can hit that mutation. I think that’s sort of the Holy Grail of what we want to do in oncology, but it is a little bit cumbersome. I think we’re going to have a NCI [National Cancer Institute]—sponsored study trying to look at that kind of an approach, which I think is very welcome. But for now, I don’t think I’m going to be switching out of alectinib to anything else.

H. Jack West, MD: So just pulling it back to the first-line diagnosis, we have alectinib. We have ceritinib, and we have data that look strong for brigatinib. How do you weigh the choices?

Charu Aggarwal, MD, MH: I think alectinib is still my favorite approach, just because I have more experience using it. I think the adverse effect profile is…I mean, I can’t compare alectinib and brigatinib head-to-head. There have been slightly higher reports of pneumonitis with brigatinib, but I do think that given the history of using alectinib over the past couple of years, at least we’ve become comfortable with it and the data support it. So I’m more favored to use that in the frontline, even though the brigatinib data compared with crizotinib look pretty good.

H. Jack West, MD: I think brigatinib looks quite strong, but that’s against crizotinib, which is definitely a weaker competitor than alectinib by a long shot. It has very good CNS activity, but we know that the second-generation agents, including alectinib, broadly do have that. And the pneumonitis risk, though it’s 3% or 4%, is more of a consideration than alectinib would be. I think that maybe with much longer follow-up, if brigatinib looks like it has efficacy that lasts far longer, that could possibly differentiate from alectinib. But you just can’t know that from the initial analysis where, yes, it looks better at a year. That doesn’t even speak to the issue of our current standard of care of alectinib. We’ve just moved on, I would say.

Transcript Edited for Clarity

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