Assay Finds Patients Who Will Benefit From Adjuvant Chemotherapy in Early-Stage NSCLC

Biomarker testing for early-stage patients with nonsquamous non–small cell lung cancer (NSCLC) allowed investigators to find and treat those patients who would benefit from chemotherapy after surgery, even though traditional guidelines would not suggest it.

The result? Patients who were treated were 78% less likely to see their disease return compared with a similar group not given chemotherapy.

David R. Spigel, MD | Image credit: Sarah Cannon Research Institute

Results of the AIM-HIGH study (NCT01817192), being presented Saturday at the American Society of Clinical Oncology (ASCO), highlight how precision medicine approaches are gaining as much notice as advances in therapy, as clinicians can identify discrete groups of patients who might benefit from treatments that would not have been tried just a few years ago.

David Spigel, MD, chief scientific officer at Sarah Cannon Research Institute, shared results from an international, multicenter, prospective randomized trial, which used a 14-gene molecular assay to select high-risk patients with stage IA-IIA NSCLC who would be candidates for adjuvant chemotherapy.

As Spigel explained in a press conference, “Adjuvant therapy, although used commonly in the treatment of non–small cell lung cancer, is not recommended for stage IA disease, and is often deferred in stages IB and stage II.”

Molecular testing, however, might reveal which patients have high-risk features beyond what can be seen in the tumor itself. The approach was so successful that at 24 months, disease-free survival (DFS) was 96% (95% CI, 0.92-1.00) for those who received adjuvant chemotherapy vs 79% (95% CI, 0.70-0.90) of patients in the observation group. Neither arm reached median DFS.

“This is the first prospective, randomized trial to show improvement in DFS with a molecular-risk discriminator in stage IA through stage IIA nonsquamous non–small cell lung cancer,” Spigel said during a press conference ahead of ASCO. He said that using this 14-gene assay to pinpoint who should have adjuvant therapy “may substantially reduce rates of early recurrence and death.”

Lung cancer causes more cancer deaths than any other type in the US. According to the National Cancer Institute, 226,650 new cases of lung cancer are diagnosed in the US every year, including about 70,000 diagnosed as stage I or stage II NSCLC. Roughly 70% of those with NSCLC have nonsquamous disease, such as adenocarcinoma and large cell carcinoma.

With lung cancer screening now recommended for at-risk patients in the US, more cases are being found when patients can be treated with surgery. Clinicians weigh a number of factors, such as cancer stage and tumor size, to decide who should have therapy before or after surgery to keep cancer from returning.

However, 5-year DFS rates remain at 65%, so methods to select other patients who might benefit from treatment after surgery were needed. This is where molecular testing can find changes in genes, proteins, and other markers that signify higher risk.

Spigel outlined the methodology for the study. Investigators used RiskReveal, a 14-gene expression profile, to identify patients at stage IA-IIA with nonsquamous NSCLC who night benefit from adjuvant therapy. Of 194 patients who were evaluable at the time of an interim analysis, 87 were randomized to receive therapy after surgery, while 107 were placed in an observation group. In both arms, 55% of the patients had stage IA disease. Demographics and tumor characteristics between the 2 groups were well balanced.

After a median follow-up of 19.6 months in the chemotherapy group and 19.0 months in the observation group, the HR for risk of disease recurrence or death in the chemotherapy arm was 0.22 (95% CI, 0.06-0.76; P = .0087).

Charu Agrawal, MD, MPH | Image credit: Penn Medicine

Discussant Charu Agrawal, MD, Leslye M. Heisler Professor of Lung Cancer Excellence at Penn Medicine, concurred with Spigel’s assessment that there is a need to find patients who aren’t receiving adjuvant therapy, “yet we know that they are high risk.”

“These early interim results from this very promising, prospective randomized study will help us lay the foundation for precision therapy in early-stage non–small cell lung cancer,” she said, predicting that in addition to traditional assays, clinicians would have help from artificial intelligence solutions to better stratify patients.

“In the future, we may even be able to add personalized vaccines after we identify high-risk disease,” Agrawal said.

Reference

Spigel DR, Westeel V, Anderson IC, 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. J Clin Oncol. 2025;43(suppl 17). doi:10.1200/JCO.2025.43.17_suppl.LBA8027