Phase III Trials Test First-Line Options in Advanced NSCLC.

In advanced NSCLC with EGFR exon 20 insertions, PAPILLON and REZILIENT3 showed amivantamab plus zipalertinib significantly improved progression-free survival as first-line therapy.

• Why it matters: First-line options for EGFR exon 20 insertion–positive advanced NSCLC are needed to improve outcomes, but overall survival benefits can be obscured by treatment crossover.
• What they did: Two phase III trials, PAPILLON and REZILIENT3, tested amivantamab and zipalertinib combination therapies in this EGFR exon 20 insertion subgroup, measuring progression-free survival and overall survival.
• The result: Progression-free survival improved significantly, but high crossover rates prevented demonstrating an overall survival benefit, limiting conclusions about survival advantage.

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