VIDEO: ‘Flurry of activity’ in treatment space for EGFR-mutated lung cancer

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So, there's actually just been an absolute flurry of activity in recent years, and especially in the last year with regards to new treatment options for our patients with EGFR lung cancer. So, I mean, to start with, just within the stage four setting, there have been two additional FDA approvals in the frontline that includes a combination of osimertinib (Tagrisso; AstraZeneca) plus chemotherapy. These were data that was actually presented at last year's World Lung Meeting where they looked at platinum-based chemotherapy combined with osimertinib as compared to osimertinib alone. And they found a significant progression-free survival benefit with this combination. There's also a strong trend thus far. However, we're still waiting on kind of mature overall survival data, but there is the data thus far strongly suggests that there's likely gonna be an overall survival benefit as well with this combination of osimertinib plus chemotherapy. The other thing I wanna highlight about this particular regimen is that there was a benefit kind of really irrespective of the subgroups analyzed, including those patients with L858R mutated tumors, as well as those patients with underlying CNS disease at diagnosis. So, there is a significant progression-free survival benefit with the combination of osimertinib plus platinum-based chemotherapy.

However, it's also kind of important to keep in mind with this particular regimen is that there are more toxicities associated as one would expect kind of the standard chemotherapy-related side effects that one would expect with chemotherapy. And also, we've gotten very used to giving osimertinib to our patients with eGFR disease when they're first diagnosed. It's very well tolerated. It's highly effective for many patients for an extended period of time. And they can just take this at home, and they can see us in clinic every once or two months. But of course, if you incorporate an IV medicine like chemotherapy, certainly you're spending more time in the infusion room, you're coming to the infusion room every three weeks, you're coming to clinic every three weeks. And of course, that kind of changes the way the therapy is given to our patients. So certainly, things to kind of all keep in mind.

Another significant recent FDA approval is the combination of a third-generation TKI, Lazertinib (Lazcuse; Janssen Biotech, Inc.), plus a bispecific antibody called amivantamab (Rybrevant; Janssen Biotech, Inc.). And so, lazertinib, like I said, is a third-generation TKI. It's really not too dissimilar from osimertinib. Amivantamab is a bispecific antibody that targets both MET and EGFR. And from the MARIPOSA study, what they found was that there was a significant progression-free survival benefit with a combination of amivantamab plus lazertinib as compared to osimertinib alone. Again, there is immature OS data at this time. However, there is a strong suggestion that there will be an overall survival benefit with this combination as compared to osimertinib. And again, of course, while there are the additional progression-free survival benefits with this particular combination, and there's also good CNS data with this particular combination. We know that lazertinib as a third-generation TKI does have good CNS penetration just by itself, but there's also a lot of data strongly supporting Amivantamab and its level of CNS activity.

So, while there are those benefits, there are also certain toxicities we need to kind of keep in mind with this regimen as well. In particular, things like infusion reactions are very much real. In fact, in the original MARIPOSA study, about 60 to 65% of patients did experience an infusion reaction, especially with some of those earlier doses. There are more recent data with regards to kind of the Skipper study, which suggested that giving two or three days of dexamethasone as premedication up front can significantly decrease the risk for infusion reactions. But then also kind of other more chronic toxicities to really keep in mind with amivantamab is the risk for rash, as well as paronychia and lower extremity edema. So, there's a lot of very encouraging data with all these regimens that are now FDA approved.

And thankfully, we now kind of practice in a space where we have more than one option for our patients with newly diagnosed EGFR disease. And it really comes down to having a very nuanced conversation with our patients as far as the potential benefits of more intensive therapies as well as kind of keeping in mind kind of these new associated toxicities that come with these more intensive therapies. So, like I said, we have a number of really good options for our patients now with newly diagnosed EGFR kind of stage four disease. And so that's just really just in the stage four setting.

I mean, as far as other things that have happened within the EGFR space, there's been also a lot of activity and within the earlier stage setting. Of course, I think nearly everyone in oncology know about the results of the Dura study and have incorporated the use of osimertinib in their practice after surgical resection. But then there's also recent data from the Laura study that were presented at this last year ASCO looking at the use of osimertinib in the stage three locally advanced setting and giving that after chemotherapy and radiation. And what this study found that there was a significant progression-free survival benefit of giving indefinite osimertinib after finishing chemotherapy radiation as compared to placebo in patients with EGFR disease. And a couple of things I really wanna highlight from the Laura study is the fact that in particular, those patients who are randomized placebo group, man, did they do really poorly. EGFR disease in this context is very much a beast. And in some ways, locally advanced EGFR disease is almost kind of like a stage, a mini stage four lung cancer. And it really kind of points to the fact that it is important to get our patients with eGFR disease after they finish chemo RT on the proper targeted therapy, which is osimertinib. And this is now an also an FDA approved option for patients as of this past September.