- Design
- phase 3, international, randomised, open-label trial with blinded independent central review and permitted crossover (WU-KONG28)
- Population
- 324 patients with advanced nonsquamous NSCLC harbouring EGFR exon 20 insertion mutations, untreated
- Primary outcome
- progression-free survival by blinded independent central review
- Effect
- median 10.3 vs 7.5 months (HR 0.65; 95% CI 0.50-0.85; P<0.001); 12-month progression-free survival 46.1% vs 26.7%; objective response 58.9% vs 31.1%; grade 3 or higher adverse events 75.5% vs 56.7%
WU-KONG28 randomised 324 patients with advanced nonsquamous non-small-cell lung cancer carrying EGFR exon 20 insertion mutations to oral sunvozertinib or carboplatin-pemetrexed chemotherapy, with crossover permitted after confirmed progression. Median progression-free survival by blinded central review was 10.3 months against 7.5, a hazard ratio of 0.65.
The response figures are the more tangible ones for a clinic conversation. Objective response was 58.9% against 31.1%, median best change in tumour size -42.1% against -24.7%, and median duration of response 11.2 months against 7.1. Overall survival data were immature at 38.9%.
Exon 20 insertions have been the awkward corner of EGFR-mutant lung cancer — resistant to the usual tyrosine kinase inhibitors, leaving chemotherapy as the default first line long after other EGFR subtypes moved on. This moves that group into the same pattern as the rest.
Toxicity is not trivial and should not be presented as the gentler option. Grade 3 or higher adverse events occurred in 75.5% of the sunvozertinib group against 56.7% on chemotherapy, most commonly raised creatine kinase, diarrhoea and anaemia, though no deaths were attributed to sunvozertinib.
The prerequisite is testing. An exon 20 insertion is not detected by the common single-gene EGFR assays used in much of Indian practice, and a patient who is never tested for it cannot benefit from any of this.
- Use a broad panel or an assay that specifically covers exon 20 insertions; common EGFR hotspot tests miss them
- Offer sunvozertinib first line where an exon 20 insertion is confirmed and the drug is obtainable
- Warn about diarrhoea and check creatine kinase; grade 3 or higher events were commoner than with chemotherapy
- Discuss that overall survival data are not yet mature, and that crossover was permitted
- Where the drug is unavailable, carboplatin-pemetrexed remains the comparator this was tested against
The statistics, in plain English
The hazard ratio of 0.65 (95% CI 0.50-0.85) for progression or death means roughly a third fewer events, and the median difference of 2.8 months understates it: at 12 months, 46.1% of the sunvozertinib group were progression-free against 26.7% on chemotherapy, which is the more informative way to read a survival curve than its midpoint. Overall survival at 38.9% maturity means fewer than two in five of the required deaths have occurred, so no survival conclusion is possible; crossover after progression will also dilute any survival difference that exists. Progression-free survival was assessed by blinded independent central review, which matters in an open-label trial where investigator assessment could be influenced by knowing the allocation.
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