Mobocertinib Use in Platinum-Pretreated Patients With EGFR Exon 20 Insertion–Positive mNSCLC - Episode 4
In the context of mobocertinib clinical data, experts consider factors that help them select therapy and manage therapy for patients with EGFR exon 20 insertion–positive mNSCLC.
Gregory Riely, MD, PhD: We’ve gone through some of the meat of the paper. One thing we haven’t talked about is the general therapeutic landscape. What do you see as key takeaways from this paper?
Tarek Mekhail, MD: We have a targeted drug for EGFR [estimated glomerular filtration rate] exon 20 insertion that we didn’t have before. EGFR exon 20 insertion is a peculiar disease that has poor outcome with any therapy you give, and it doesn’t respond to prior TKIs [tyrosine kinase inhibitors]. I don’t like to give immune checkpoint inhibitors as a frontline [therapy] for these patients, so I typically give a platinum doublet alone. Some of my partners would add an antiandrogenic. After that, we’re stuck. We didn’t have good therapy in the past. We’ve tried many things and certainly supported by some small studies doubling the dose of osimertinib. But now we have a targeted drug, and it’s not the only 1. There’s amivantamab, which is also approved. There are other drugs in the pipeline. You might comment on them. But the takeaway message is that we have 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 say it. The majority of patients have some response, some benefit, but a significant minority have a great response and a very long duration of benefit. When I think about the therapeutic landscape, I agree completely with your approach. When I meet a patient, who has an EGFR exon 20 insertion, as initial therapy, we talk about platinum doublet chemotherapy. I’m typically giving carboplatin pemetrexed for these folks, or maybe cisplatin pemetrexed if they’re younger. At the second-line treatment decision, we have that decision point between amivantamab and mobocertinib. Mobocertinib has the advantage of being an oral agent, but amivantamab has the advantage of being an IV [intravenous] agent, so they don’t have to worry about between visits. I find myself talking about both these drugs with patients because ultimately neither treatment has a curative effect. We’re probably going to be thinking about the other drug down the road. How do you approach that second-line decision around mobocertinib vs amivantamab?
Tarek Mekhail, MD: In all honesty, when I compare the studies—which is something we say we shouldn’t do, but we do all the time—they’re almost equally effective. Perhaps amivantamab has a little higher response rate. Numerically the trade-off is shorter, with median duration of response. I already told you my bias about 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 adverse-effect profile. With the amivantamab you have the infusion reactions. With mobocertinib you have the diarrhea, and it all comes down to which drug you’re more familiar with. I’m more familiar with mobocertinib because I participated in the study. I can envision that people who participated in amivantamab studies are more familiar with amivantamab. Patients are stuck with whichever 1 their physician is more familiar with. I wish I knew the sequencing, but I know for sure that drugs might not work on the same patient. I’m optimistic that 1 drug might work after the other, even though 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’re different patients, and we need to figure this out at some point.
Gregory Riely, MD, PhD: I completely agree. This is going to require some real-world data to understand how patients who start with 1 and go to the other and then other patients start with the other and go to the other. Looking at those outcomes, we come from this world of tyrosine kinase inhibitors. We learned a lot about mechanisms of resistance, back to the erlotinib days, and then we had to go from erlotinib to osimertinib. We can’t go from osimertinib to erlotinib. Clearly, these drugs have 2 very different mechanisms of action, so we’re not seeing that same thing. It’s going to be interesting to see how these data come together, but we’ll definitely need to get that data over the coming year or 2.
Transcript edited for clarity.