Aumolertinib with radiotherapy beat chemoradiotherapy in stage III EGFR-mutant lung cancer — in a small, stopped trial

Design

Phase 3 open-label randomised trial, stopped early; plus real-world cohort

Population

43 patients with unresectable stage III EGFR-mutant NSCLC (plus 125 real-world)

Primary outcome

Progression-free survival

Effect

Median 34.0 vs 7.4 months; HR 0.15 (P < 0.001); OS HR 0.32 (P = 0.09)

ADVANCE was a phase 3 trial in unresectable stage III non-small-cell lung cancer with EGFR mutations, comparing aumolertinib 110 mg daily with definitive radiotherapy against cisplatin–pemetrexed chemoradiotherapy. It planned 98 patients but was stopped early after 43, because of slow accrual, loss of equipoise and a large interim difference.

At a median follow-up of 25.5 months, median progression-free survival was 34.0 months with aumolertinib and 7.4 months with chemoradiotherapy (HR 0.15). Overall survival was not reached vs 30.5 months (HR 0.32, P = 0.09). Neutropenia and nausea were less frequent and quality of life better with aumolertinib. A prespecified real-world cohort of 125 patients gave supporting results.

Early stopping with 43 patients almost always inflates the effect size. The direction is consistent with other evidence for EGFR inhibitors in stage III disease, but this trial alone cannot define a new standard. Aumolertinib is a third-generation EGFR inhibitor developed in China; its availability in India is not established here.

• Test all unresectable stage III non-squamous lung cancers for EGFR mutations before planning definitive treatment.
• Discuss EGFR inhibitor strategies in stage III EGFR-mutant disease at the multidisciplinary meeting.
• Treat this trial as supportive rather than definitive, because it stopped early at 43 patients.
• Overall survival difference was not statistically significant.

Why it matters

It adds to the case for moving targeted therapy into stage III EGFR-mutant disease.

Don't overread it

The trial stopped early after randomising 43 of 98 planned patients; the effect size is likely inflated.

The statistics, in plain English

A hazard ratio of 0.15 suggests an 85% reduction in progression risk, but trials stopped early for benefit with small numbers tend to overestimate effects. The overall survival P value of 0.09 is not significant.

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