N Engl J Med
ASCO 2026: Oral targeted therapy beats chemo in hard-to-treat lung cancer
Clinical Takeaway: For patients with advanced NSCLC harboring EGFR exon 20 insertion mutations, first-line sunvozertinib significantly improved progression-free survival and response rates versus platinum-pemetrexed chemotherapy, supporting its use as a new frontline treatment option.
Patients with advanced NSCLC harboring EGFR exon 20 insertion mutations have historically faced poor outcomes and limited treatment options, but results from the phase 3 WU-KONG28 trial, presented at ASCO 2026 and published in the New England Journal of Medicine, show that the oral EGFR-targeted therapy sunvozertinib significantly outperformed standard platinum-based chemotherapy when used as first-line treatment.
The multinational study randomized 324 treatment-naïve patients with advanced nonsquamous NSCLC harboring EGFR exon 20 insertion mutations to receive either sunvozertinib 300 mg daily or carboplatin-pemetrexed chemotherapy. Median progression-free survival was 10.3 months with sunvozertinib versus 7.5 months with chemotherapy (hazard ratio [HR], 0.65; P<0.001). At 12 months, 46.1% of patients receiving sunvozertinib remained progression-free compared with 26.7% of those receiving chemotherapy.
Tumor responses were also substantially higher with the targeted agent. Objective response rates reached 58.9% with sunvozertinib versus 31.1% with chemotherapy, while median duration of response was 11.2 months versus 7.1 months, respectively. Notably, more than 90% of patients whose disease progressed on chemotherapy crossed over to receive sunvozertinib, which may complicate future overall survival comparisons; survival data remain immature.
“These results show that sunvozertinib can control the disease longer and shrink tumors more often than chemotherapy, offering a new, much-needed option for those starting treatment,” said lead author John Heymach, MD, PhD.
Adverse events were generally consistent with prior studies. Grade 3 or higher events occurred in 75.5% of patients receiving sunvozertinib and 56.7% receiving chemotherapy. The most common severe toxicities with sunvozertinib included elevated creatine kinase levels, diarrhea, and anemia. Treatment-related discontinuation occurred in 7.4% of patients, and no treatment-related deaths were reported.
The findings support a shift toward targeted, chemotherapy-free first-line therapy in EGFR exon 20–mutant NSCLC, with sunvozertinib offering both improved efficacy and the convenience of an oral regimen.
Source: Zhou C, et al; WU-KONG28 Investigators. (2026, May 29). N Engl J Med. First-Line Sunvozertinib in NSCLC with EGFR Exon 20 Insertion Mutations