Dr Spigel on Adjuvant Chemotherapy in Stage IA/IIA, Molecularly Higher-Risk NSCLC

"If you have a patient in front of you with nonsquamous, non–small cell lung cancer and early-stage disease, and you're already planning to give chemotherapy, [this molecular test is not necessary]. If you know—or the patient and their family know—that they do not want chemotherapy, [this test is also not appropriate]. However, in those patients where you're not sure [if it’s a] higher-risk cancer or whether chemotherapy should be used, this is absolutely a test that can now be ordered.”

David Spigel, MD, chief scientific officer at Sarah Cannon Research Institute, discussed findings from the international, multicenter, prospective randomized AIM-HIGH trial (NCT01817192) evaluating the utility of adjuvant chemotherapy in patients with stage IA to IIA non–small cell lung cancer (NSCLC) identified as higher risk by a 14-gene molecular assay.

Findings from the study presented at the 2025 ASCO Annual Meeting demonstrated a significant disease-free survival (DFS) benefit with adjuvant chemotherapy compared with observation in patients identified as high-risk who were randomly assigned between the study’s 2 arms.

At the 24-month landmark analysis, patients treated with adjuvant chemotherapy (n = 107) achieved a 24-month disease-free survival (DFS) rate of 96% (95% CI, 92%-100%) compared with 79% (95% CI, 70%-90%) in the observation arm (HR, 0.22; 95% CI, 0.06-0.76; P = .0087). Among patients with stage IA disease, a similar benefit was observed; the DFS rate was 98% (95% CI, 94%-100%) for chemotherapy (n = 58) vs 78% (95% CI, 65%-93%) for observation (n = 48; HR, 0.15; 95% CI, 0.02-0.16; P = .0345).

The study included patients at least 18 years of age with completely resected, stage IA to IIA, primary nonsquamous NSCLC who had negative margins following resection. Risk stratification was completed using the 14-gene panel, and those with molecularly intermediate- or high-risk were randomly assigned 1:1 to chemotherapy or observation.

Spigel emphasized that this assay serves a practical role in clinical decision-making, particularly for patients with early-stage, nonsquamous NSCLC where the need for adjuvant therapy is uncertain. The assay identifies individuals at high risk for recurrence, allowing clinicians to tailor treatment plans more precisely. It is not intended for use in cases where adjuvant chemotherapy is already clearly indicated or definitively declined by the patient, he said.