Validation of the 12-gene predictive signature for Adjuvant Chemotherapy Response in Lung Cancer

Purpose: Response to adjuvant chemotherapy (ACT) after tumor resection varies widely among non-small cell lung cancer (NSCLC) patients; therefore, it is of clinical importance to prospectively predict who will benefit from ACT before starting the treatment. The goal of this study is to validate a 12-gene ACT predictive signature developed from a previous study using a clinical grade assay. Experimental Design: We developed a clinical grade assay for formalin-fixed paraffin-embedded (FFPE) samples using the NanoString nCounter platform to measure the mRNA expression of the previously published 12-gene set. The predictive performance was validated in a cohort of 207 early stage resected NSCLC patients with matched propensity score of ACT. Results: The effects of ACT were significantly different in patients from the predicted ACT benefit-group and those in the predicted ACT non-benefit group (p=0.0056 for interaction between predicted risk group and ACT). Specifically, in the predicted ACT benefit group, the patients receiving ACT had significant RFS benefit (HR=0.34, p=0.016, ACT vs non-ACT), while in the predicted ACT non-benefit group, the patients receiving ACT actually had worse RFS (HR=1.86, p=0.14, ACT vs non-ACT) than those who did not receive ACT. Conclusions: This study validated that the 12-gene signature and the FFPE-based clinical assay predict that patients whose resected lung ADCs exhibit an ACT benefit gene expression pattern and who then receive ACT have significant survival advantage compared to patients whose tumors exhibit the benefit pattern but do not receive ACT.

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