New Phase 3 data in NEJM show sunvozertinib outperformed chemotherapy as first-line treatment for advanced nonsquamous NSCLC with EGFR exon 20 insertion mutations. In the randomized trial, sunvozertinib delivered longer progression-free survival and higher objective response rates versus carboplatin–pemetrexed. Among 324 randomized patients, median progression-free survival was 10.3 months with sunvozertinib versus 7.5 months with chemotherapy. At 12 months, PFS was reported in 46.1% of sunvozertinib-treated patients compared with 26.7% in the chemotherapy arm, and the trial met its primary endpoint based on blinded independent central review. The safety profile showed higher rates of grade 3 or higher adverse events in the targeted-therapy arm (75.5% vs 56.7%). No deaths were attributed to investigators’ sunvozertinib-related adverse events. With continued follow-up, overall survival readouts will be central to how quickly this regimen moves into treatment algorithms.