Approval of Alunbrig Offers Another Option for ALK-Positive NSCLC, But More Research Is Needed

June 23, 2020

In an interview with CURE®, Dr. Pail Paik of the Memorial Sloan Kettering Cancer Center discusses the FDA approval of Alunbrig for patients with ALK-positive metastatic non-small cell lung cancer.

In late May, the Food and Drug Administration (FDA) approved Alunbrig (brigatinib) for the first-line treatment of patients with ALK-positive metastatic non—small cell lung cancer (NSCLC), as detected by an FDA-approved test. But while having more treatment options in the targeted therapy realm is a good thing, further research is needed to determine when and in what setting it should be used, according to Dr. Paul Paik of Memorial Sloan Kettering Cancer Center.

In an interview with CURE®, Paik discussed how this approval — a superior option compared to the previous standard of care of Xalkori (crizotinib) – fits within the treatment paradigm of ALK-positive NSCLC, touching on the idea that it is still too new and has not been compared against the current standard of treatment of Alecensa (alectinib) in enough settings to be the clear first treatment choice.


I think in terms of practical impact, it's a little unclear right now. Alectinib, or Alecensa, has been the standard first-line therapy for quite some time now, following (data) presentation for J-ALEX and ALEX trials, with frontline alectinib against crizotinib, and those data have looked great. And as they mature, they continue to look great. And that's been the standard of care for quite some time now, for ALK-positive lung cancer patients.

But there's no head-to-head comparison between brigatinib and alectinib; that trial has never been done. We don't know which one is sort of better, or which one should be selected over another one. So, I think from a practical standpoint, from a patient, it's unclear which one should be chosen first.

You could play the exercise of cross-comparison, understanding that there are caveats to that, to try to make some kind of decision as to what to do, and that is maybe somewhat helpful. The PFS (progression-free survival) data in particular for alectinib may be a little bit better by hazard ratio and median PFS, than brigatinib. But at the end of the day, we just don't know, because we haven't done that head to head trial. But they are both better, clearly, than crizotinib.

And so, I think practically, many of us will continue to prescribe alectinib because the experience with that has been so great in the past and because that those data are pretty mature.

There is a second line trial that's comparing brigatinib versus alectinib that's being done, so that readout should be interesting. Because if there's a signal that one is better than the other in the second line setting, that may end up informing how people operate in the first line setting.

I think that may be the closest thing to data that might help clarify that situation. But practically, it's a little bit unclear from a rigorous standpoint as to which one to use in the frontline setting.

CURE: So then in terms of just the treatment landscape in general, you touched on a few different options right now, but how does this approval kind of alter that treatment landscape for this subset?

Paik: It doesn't too much, and that's what happens when you have really great drugs that are available right at the beginning for our patients. So, it doesn't too much. It's another great drug compared to what the old standard used to be.

What I'd say is that it does raise into question what we do at the time of progression for these patients. And there's still a bit of a question with regards to that. The academic mindset is to continue to do tumor biopsies or liquid biopsy testing to look for secondary changes in ALK to try to guide therapy, based on the sensitivities or specificities for these different drugs to these mutations, but that can be hard from a practical standpoint, and that requires a certain amount of knowledge that may be hard to disseminate out into the community.

So, it still raises that question as to how to navigate those spheres. But here again, there are so many drugs that have been approved in the second line setting and beyond that there are just lots of options so it could be a matter of just picking one see if it works and rotating to the next ones after that.

It is worth mentioning also that standard chemo, even though it gets a bad name, is very good in this population also, and that we've known for quite some time also. So even then, you know, the, the chemo option for these patients is quite good.

Read CURE®’s original coverage on the approval of Alunbrig as frontline treatment for ALK-positive NSCLC.