Photo Credit: iStock.com/Mohammed Haneefa Nizamudeen
Interim results from a randomized trial suggest an assay could refine treatment decisions for patients with stage Ia–IIa non-squamous NSCLC.
An early interim analysis from a phase 3 trial suggests that a 14-gene expression profile assay can identify patients with early-stage non-squamous non-small cell lung cancer (NSCLC) who may have a substantial benefit from receiving adjuvant chemotherapy after resection. The findings were presented at the 2025 ASCO Annual Meeting.
Despite advances in surgical and systemic therapies, outcomes for early-stage NSCLC remain suboptimal, according to the study authors. Five-year disease-free survival (DFS) for patients with stage Ia NSCLC is approximately 65%, highlighting the need for better risk stratification and treatment guidance.
“Preliminary, non-randomized clinical data suggest the predictive efficacy of RiskReveal, a 14-gene expression profile, in identifying stage Ia-IIa patients with non-squamous NSCLC who benefit from adjuvant therapy,” wrote David R. Spigel, MD, and colleagues. “We undertook an international, multicenter, randomized clinical trial to confirm these findings. Here, we report the results of an early interim analysis that was planned to detect a large discrepancy in outcomes between arms.”
Patients Stratified by Risk
The study enrolled 421 patients who underwent curative resection for stage Ia–IIa NSCLC. The researchers used the RiskReveal assay to stratify patients into low-, intermediate-, and high-risk groups. Those classified as intermediate or high risk were randomly assigned to receive either four cycles of platinum-based adjuvant chemotherapy or observation alone. The modified intent-to-treat (mITT) population included patients who continued to meet eligibility criteria at randomization or the start of chemotherapy.
The researchers defined the primary endpoint, DFS, as the time from randomization to disease recurrence, excluding new primary lung cancers or death from any cause.
“DFS was compared between arms using a log-rank test and Kaplan-Meier analysis. An early interim analysis was planned with a type I error rate of 0.02,” the researchers said.
Benefit for Chemotherapy Arm
At the time of interim analysis, 194 patients were eligible for evaluation, including 87 in the chemotherapy arm and 107 in the observation arm. The authors reported that baseline characteristics, including age, sex, and tumor size (>4 cm), were well balanced between groups, with a median follow-up of approximately 19 months.
The adjuvant chemotherapy group saw a significant survival advantage at 24 months, with a DFS of 96% (95% CI, 0.92–1.00) compared with 79% in the observation arm (95% CI, 0.70–0.90). The researchers reported a hazard ratio of 0.22 (95% CI 0.06–0.76; P=0.0087)
Median DFS was not reached in either group, indicating sustained benefit over time. Based on the magnitude of effect, the study’s Data Safety Monitoring Board (DSMB) recommended halting further enrollment, although follow-up will continue to assess long-term outcomes.
“Improved survival in lung cancer is best achieved by optimizing outcomes in the earliest stages of disease. Identification of patients who benefit from adjuvant chemotherapy using this predictive test could result in a dramatic improvement in survival for the growing percentage of patients diagnosed in stages I-IIa,” Dr. Spigel and colleagues concluded.
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