EXCLAIM Cohort in the mNSCLC: Selection and Treatment Management

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Gregory Riely, MD, PhD: We’ve gone through some of the meat of the log. One thing we haven’t talked about is the general therapeutic landscape. What do you see as the main takeaways from this document?

Tarek Mekhail, MD: We have a drug targeted for EGFR [estimated glomerular filtration rate] the insertion of exon 20 that we didn’t have before. EGFR exon 20 insertion is a particular disease that has poor outcomes with any treatment you give, and it does not respond to prior TKIs [tyrosine kinase inhibitors]. I don’t like giving first line immune checkpoint inhibitors [therapy] for these patients, therefore, I generally give a platinum doublet alone. Some of my partners would add an anti-androgen. After that, we’re stuck. We didn’t have good therapy in the past. We have tried many things and certainly supported by a few small studies doubling the dose of osimertinib. But now we have a targeted drug, and it’s not the only one. There is amivantamab, which is also approved. There are other drugs in the pipeline. You could comment on them. But the take-home message is that we have a reasonably effective drug. It’s not effective in the majority, but when it works, it works.

Gregory Riely, MD, PhD: That’s a great way to put it. The majority of patients have some response, some benefit, but a significant minority have an excellent response and a very long duration of benefit. When I think of the therapeutic landscape, I completely agree with your approach. When I meet a patient, who has an insertion of exon 20 of the EGFR, in initial treatment, we speak of a platinum doublet. I usually give these people carboplatin pemetrexed, or maybe cisplatin pemetrexed if they’re younger. At the second-line treatment decision, we have this decision point between amivantamab and mobocertinib. Mobocertinib has the advantage of being an oral agent, but amivantamab has the advantage of being an intravenous agent [intravenous] agent, so they don’t have to worry between visits. I find myself talking about these two drugs with patients because ultimately neither treatment has a curative effect. We’ll probably think about the other drug down the road. How are you approaching this second-line decision regarding mobocertinib versus amivantamab?

Tarek Mekhail, MD: In all honesty, when I compare the studies—which we say we shouldn’t do, but we do it all the time—they’re almost as effective. Amivantamab may have a slightly higher response rate. Numerically, the trade-off is shorter, with a median response time. I’ve already told you my bias on the median duration of response, but the message is that both drugs have an adverse effect profile that needs to be well managed. It’s a completely different side effect profile. With amivantamab, you have the infusion reactions. With mobocertinib, you get diarrhea, and it all depends on which drug you know best. I know mobocertinib better because I participated in the study. I can imagine that people who have participated in amivantamab studies are more familiar with amivantamab. Patients are stuck with the one their doctor is most familiar with. I would like to know the sequencing, but I know for sure that the drugs may not work on the same patient. I’m optimistic that one drug after another can work, although we don’t have enough data because I don’t think the 25% who responded to mobocertinib are the same 30% or so who responded to amivantamab. They are different patients, and we have to understand that at some point.

Gregory Riely, MD, PhD: I completely agree. This is going to require real-world data to understand how patients who start with 1 and go to the other, and then other patients start from the other and go to the other. Looking at these results, we come from this world of tyrosine kinase inhibitors. We learned a lot about resistance mechanisms, in the erlotinib era, and then we had to switch from erlotinib to osimertinib. You can’t switch from osimertinib to erlotinib. Clearly, these drugs have 2 very different mechanisms of action, so we don’t see the same thing. It’s going to be interesting to see how this data comes together, but we’ll definitely need to get this data over the next year or 2.

Transcript edited for clarity.

Martin E. Berry