Validation of the 12-gene Predictive Signature for Adjuvant Chemotherapy Response in Lung Cancer.

Abstract

PURPOSE:

Response to adjuvant chemotherapy after tumor resection varies widely among patients with non-small cell lung cancer (NSCLC); therefore, it is of clinical importance to prospectively predict who will benefit from adjuvant chemotherapy before starting the treatment. The goal of this study is to validate a 12-gene adjuvant chemotherapy 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 patients with early-stage resected NSCLC with matched propensity score of adjuvant chemotherapy.

RESULTS:

The effects of adjuvant chemotherapy were significantly different in patients from the predicted adjuvant chemotherapy benefit group and those in the predicted adjuvant chemotherapy nonbenefit group (P = 0.0056 for interaction between predicted risk group and adjuvant chemotherapy). Specifically, in the predicted adjuvant chemotherapy benefit group, the patients receiving adjuvant chemotherapy had significant recurrence-free survival (RFS) benefit (HR = 0.34; P = 0.016; adjuvant chemotherapy vs. nonadjuvant chemotherapy), while in the predicted adjuvant chemotherapy nonbenefit group, the patients receiving adjuvant chemotherapy actually had worse RFS (HR = 1.86; P = 0.14; adjuvant chemotherapy vs. nonadjuvant chemotherapy) than those who did not receive adjuvant chemotherapy.

CONCLUSIONS:

This study validated that the 12-gene signature and the FFPE-based clinical assay predict that patients whose resected lung adenocarcinomas exhibit an adjuvant chemotherapy benefit gene expression pattern and who then receive adjuvant chemotherapy have significant survival advantage compared with patients whose tumors exhibit the benefit pattern but do not receive adjuvant chemotherapy.

• Authors: Yang Xie, Wei Lu, Shidan Wang, Ximing Tang, Hao Tang, Yunyun Zhou, Cesar Moran, Carmen Behrens, Jack A Roth, Qinghua Zhou, David H Johnson, Stephen G Swisher, John V Heymach, Vassiliki A Papadimitrakopoulou, Guanghua Xiao, John D Minna, Ignacio I Wistuba
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 25 Issue 1 Pg. 150-157 (01 01 2019) ISSN: 1557-3265 [Electronic] United States
• PMID: 30287547 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: ©2018 American Association for Cancer Research.

Chemical References

• Biomarkers, Tumor
• Neoplasm Proteins

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols
• Biomarkers, Tumor
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, pathology)
• Chemotherapy, Adjuvant
• Disease-Free Survival
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Male
• Middle Aged
• Neoplasm Proteins (genetics)
• Neoplasm Staging
• Paraffin Embedding
• Prognosis
• Retrospective Studies
• Risk Factors
• Transcriptome (drug effects)
• Treatment Outcome