A NEW interim analysis from the AIM-HIGH trial confirms that a 14-gene expression profile can identify patients with early-stage non-squamous non-small-cell lung cancer (NSCLC) who benefit from adjuvant platinum-based chemotherapy.
Despite improvements in screening and surgical approaches, survival for patients with Stage IA–IIA NSCLC remains low, and current guidelines recommending adjuvant treatment in Stages IB and IIA lack validated criteria to predict benefit. This multicentre, randomised Phase 3 trial enrolled patients from 45 sites across France, Germany, and the USA. Adults with Stage IA–IIA non-squamous NSCLC underwent risk stratification using a CLIA-certified 14-gene assay. Those classified as molecular high risk (either high or intermediate scores) were randomised 1:1 to receive four cycles of adjuvant platinum-based chemotherapy or observation. This prespecified interim analysis assessed disease-free survival at 24 months in the modified intention-to-treat (mITT) population.
Of 449 enrolled patients, 236 with high-risk molecular profiles were randomised, and 200 formed the mITT cohort. Among these, 87 patients received chemotherapy and 107 were observed. The two arms were balanced in sex and disease stage. At 24 months, disease-free survival was significantly higher in the chemotherapy group at 96% (95% CI: 92–100), compared to 79% (70–90) in the observation group. This corresponded to a hazard ratio of 0.22 (95% CI: 0.06–0.76; p=0.0087). Six deaths had occurred at the time of analysis. No unexpected safety signals were reported, and chemotherapy regimens were in line with institutional standards of care.
These results indicate that gene expression profiling can effectively stratify early-stage NSCLC patients by risk and guide the use of adjuvant therapy. This approach could substantially improve disease-free survival in a population historically characterised by suboptimal long-term outcomes.
Reference
Spigel DR et al; AIM-HIGH investigators. Adjuvant chemotherapy for stage IA-IIA non-squamous, non-small-cell lung cancer identified as molecular high-risk by a 14-gene expression profile (AIM-HIGH): an international, randomised, phase 3 trial. Lancet Respir Med. 2025; DOI: 10.1016/S2213-2600(25)00213-9.
