David Spigel, MD, Sarah Cannon Research Institute, Nashville, TN, discusses the results from the AIM-HIGH study. This international, multicenter, randomized clinical trial aimed to confirm the predictive efficacy of the 14-gene expression profile, RiskReveal, in identifying stage Ia to IIa patients with non-small cell lung cancer (NSCLC) who benefit from adjuvant therapy. 

Dr Spigel concluded, “This assay can be used to help patients understand their risk of their cancer coming back and what benefits there might be with chemotherapy ... I think this provides some information to make an informed decision and I think patients not only deserve, but will want that as they look to making the best decisions in their own care."

This data was first presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

Transcript:

Hello, I'm David Spiegel. I'm a medical oncologist and am the Chief Scientific Officer at Sarah Cannon Research Institute in Nashville, Tennessee, just back from ASCO 2025 in Chicago, where we were excited to present our trial called the AIM-HIGH study.

This study was designed to explore the role of chemotherapy and a prognostic test in patients with early stage non-squamous non-small cell lung cancer. As a way of background, we use chemotherapy now traditionally in stage III, non-small cell lung cancer. In stage II disease and in some stage I settings after surgery, we discuss with patients the role of adjuvant chemotherapy and we administer usually 4 cycles of platinum-doublet chemotherapy. The absolute benefit in most patients is about 5%, and there's some controversy about whether that benefit is really reasonable in folks who have low-risk disease: those with stage I disease and those even with stage IIa disease, could there be a better way to risk stratify patients to determine if they need chemotherapy or not? That's really the rationale for this study.

A 14 gene classifier was developed called RiskReveal. This is an assay that was validated in over 1 500 patients several years ago with non-squamous non-small cell lung cancer. This was the assay that was used to risk-stratify patients in the AIM-HIGH trial. The way it worked is all patients with stage Ia, Ib and stage IIa non-squamous non-small cell lung cancer had surgery and then were risk-stratified based on this 14-gene assay. If you had low-risk disease, then you were not included in this study because your chances of doing well are so high, greater than 95% in previous validation studies. But if you were intermediate- or high-risk, you were then randomized to 4 cycles of platinum-doublet chemotherapy based on the histology of the tumor or observation. Patients were then followed with a primary end point of disease-free survival [DFS].

This study was stopped early by the Data Safety Monitoring Board because of an overwhelming advantage at the 24-month DFS landmark endpoint. The hazard ratio in favor of benefit was 0.22 in the experimental arm, or said another way, those patients with intermediate- to high-risk early-stage non-squamous non-small cell lung cancer had a 78, seven eight, 78% reduction in the risk of cancer coming back or dying from cancer compared with the group that was observed. Those were the major findings, it's the reason the trial was stopped early.

This assay is commercially available. It is covered by insurance, and it can be used now with patients to help them make better or more informed decisions. A patient today in clinic that has a non-squamous non-small cell lung cancer that is stage Ia, Ib, or  IIa, I think this tool, this assay can be used to help patients understand their risk of their cancer coming back and what benefits there might be with chemotherapy. If a patient, a doctor, the family, all have made a decision on chemotherapy, there's really no reason for this assay to be used. Likewise, if there's a decision where they're not doing chemotherapy because they don't want it, the physician doesn't recommend it, and they're very kind of hard and fast about that, this is not an assay I'd recommend using.

However, for most patients and clinical settings in between, I think this provides some information to make an informed decision. And I think patients not only deserve, but will want that as they look to making the best decisions in their own care. And that is it, I appreciate the time to talk about AIM-HIGH.

Source:

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 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract LBA8027.