WCLC 2026 | NSCLC with EGFR exon 20 insertions at WCLC 2026: PAPILLON & REZILIENT 3

Highlights from World Lung so far this year, well, there have been many, but I think in this morning’s presidential session, which is the second presidential session, we’ve heard two really interesting data sets being released. This is about EGFR exon 20 insertion lung cancer. This is an unusual EGFR mutation, and people need to remember this is usually not sensitive to traditional osimertinib-based treatments. So what do we know about this? Well, we already know we’ve got results of the Papillon study. This came out a couple of years ago, showing that if you add amivantamab to chemotherapy, we improve progression-free survival. But when that data came out, we were still waiting for the overall survival data, and it’s the overall survival data we heard today. We’ve also had previously, in fact this summer, results of the Wukong study, that is of sunvozertinib by itself, in EGFR-exon 20 insertion lung cancer, and that showed a progression-free survival as well. But the immature OS meant it wasn’t analyzed. So today we’ve heard the updated overall survival data from Papillon, that’s the amivantamab study. And what that shows is the hazard ratio for overall survival is 0.87, which is there. It’s perhaps a little disappointing. And I think the reason for that, or at least one of the reasons for that, is there was a lot of crossover in the studies. So if you had got first-line amivantamab in part of your treatment, that was great. If you had randomized the control arm, you were able to have amivantamab as crossover. And the majority of patients, in fact around 76%, got amivantamab in crossover. What that means is that the overall survival can be drowned out. So they undertook an additional exploratory analysis compensating for that crossover and came up with an overall survival hazard ratio of about 0.57. So I think that’s interesting, but I think it is exploratory. I think we have to be a little bit careful interpreting that. We then move on to the other data set, which was the REZILIENT study. This is of a drug called zipalertinib. It’s been given with chemotherapy. And what we found today was, again, a progression-free survival benefit and immature overall survival data, perhaps as we would expect. One thing we noticed in the data this morning from REZILIENT is quite a high rate of toxicity, particularly grade 3 toxicities, mainly myeloid suppression, but also some other signals as well. And there were around nine adverse event-related deaths, the details of which weren’t immediately clear. So where does that leave us? We’ve got three potential options for EGFR exon 20 insertion lung cancer beyond just standard chemotherapy. We have Papillon, that’s reimbursed in many countries, including the UK, and that’s probably got the most robust data at the moment in terms of overall survival. We have the Sunvozertinib data, has the advantage of just being a TKI, that is waiting for its overall survival data and we look forward to seeing that. And now we have REZILIENT, which has quite impressive progression-free survival data, waiting for its overall survival data, but we do have that question about toxicity. So we’re going to wait for the data to come through, but I think it’s great that we have three potential new options for this rarer EGFR subtype, for which until recently we’ve actually had very few treatments.

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