Dr Spigel Covers the AIM-HIGH Trial in Early NSCLC

David Spigel, MD, medical oncologist and the chief scientific officer at Sarah Cannon Research Institute in Nashville, Tennessee, discusses the pivotal findings from the AIM-HIGH trial (NCT01817192), a study poised to reshape how clinicians approach adjuvant chemotherapy in early-stage non-squamous non–small cell lung cancer (NSCLC).

The AIM-HIGH trial was designed to determine whether molecular risk stratification could more accurately guide treatment decisions in patients with stage IA, IB, or IIA NSCLC following surgical resection. Traditionally, early-stage lung cancer is managed with surgery alone, with adjuvant platinum-based doublet chemotherapy reserved for those with higher-risk features. However, decisions about chemotherapy in patients with stage I or II disease can be challenging, as traditional risk markers like tumor size, nodal involvement, and margin status may not provide a complete picture.

To address this, researchers employed a 14-gene expression classifier—originally validated in over 1,500 patients a decade ago—as a more sophisticated tool for assessing recurrence risk. After surgery, patients underwent molecular profiling. Those identified as low risk were excluded from randomization due to their high likelihood (95% or greater) of cure with surgery alone. Patients with intermediate or high-risk gene expression profiles were randomized to receive either four cycles of adjuvant chemotherapy or observation.

The trial was designed to evaluate disease-free survival, but was halted early by the Data Safety Monitoring Board due to overwhelming evidence of benefit in the chemotherapy group.

“The 2-year disease-free survival hazard ratio was 0.22—or in other words, there was a 78% reduction in the risk of cancer returning or dying in those patients with intermediate or high-risk disease who received chemotherapy compared with just being observed,” Spigel explains.

These findings support the growing role of precision oncology in early-stage NSCLC and may pave the way for broader use of gene expression classifiers in guiding adjuvant therapy decisions, potentially sparing low-risk patients from unnecessary toxicity while ensuring high-risk patients receive effective treatment.

“This study was stopped early. It was kind of a major result, and that’s where we’re at today,” adds Spigel.

REFERENCE:

Spigel D, Westeel V, Anderson I, et al. An international, multicenter, prospective randomized trial of adjuvant chemotherapy for stage IA-IIA non-small cell lung cancer identified as high-risk by a 14-gene molecular assay. Presented at the 2025 American Society of Clinical Oncology press briefing. May 27, 2025. Abstract LBA8027.