Investigators from the four pivotal adjuvant NSCLC trials (IALT, CALGB 9633, JBR.10, ANITA) formed the Lung Adjuvant Cisplatin Evaluation (LACE)-Bio-I consortium to conduct cross-validation/pooled meta-analyses of biomarkers that each group had identified on collected formalin fixed tumor (FFPE) to confirm their robustness/utility in a larger dataset. LACE-Bio-I had a focus predominantly on immunohistochemical methods (IHC) and single gene analyses. JBR.10 also collected fresh frozen tumor (FFT) and normal lung in a subset of patients and has identified an mRNA expression signature that is strongly prognostic and may be predictive of benefit from cisplatin/vinorelbine ACT. With the ongoing cancer genome sequencing efforts in lung cancer and the reporting of identification of novel genetic aberrations that represent crucial "oncogenic drivers" in NSCLC, we also urgently need a more adaptive strategy to explore the value of these new markers as prognostic and predictive markers in early stage patients. LACE-Bio-II has a new strategic direction. We will explore novel markers that are nucleic acid based, including gene copy number changes (amplifications and deletions), somatic gene mutations, and RNA-based markers that may involve multi-gene mRNA signatures. Using LACE-Bio FFPE tumor samples, we plan to validate the JBR.10 15-gene prognostic and predictive mRNA signature, evaluate the prognostic and predictive values of known potential oncogenic mutations, and explore the prognostic and predictive values of gene copy variations. We will also identify and evaluate the prognostic and predictive value of novel genomic aberrations discovered by Next Generation Sequencing on snap-frozen JBR.10 samples. New high performance and sensitive technologies for assaying and quantifying genomic aberrations using nucleic acid materials derived from FFPE samples have been developed and been introduced into Clinical Laboratory Improvement Amendments (CLIA)-approved laboratories. Should our strategy be successful, identified and validated markers can be rapidly introduced into clinical practice.

Public Health Relevance

The goal of LACE-Bio-II is to find and test tissue-based 'biomarkers'which can identify patients who will benefit from adjuvant chemotherapy (ACT) in addition to surgery for their early stage, resectable non-small cell lung cancer (NSCLC);and/or, identify patients who are unlikely to benefit, but who would only experience toxicity from chemotherapy, allowing patients to make informed choices about their best treatment options.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
4R01CA165958-02
Application #
8530132
Study Section
Cancer Biomarkers Study Section (CBSS)
Program Officer
Kim, Kelly Y
Project Start
2012-08-14
Project End
2017-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
2
Fiscal Year
2013
Total Cost
$417,115
Indirect Cost
$30,897
Name
Queen's University at Kingston
Department
Type
DUNS #
207884032
City
Kingston
State
ON
Country
Canada
Zip Code
K7 3-N6
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Tsao, Ming-Sound; Marguet, Sophie; Le Teuff, Gwénaël et al. (2015) Subtype Classification of Lung Adenocarcinoma Predicts Benefit From Adjuvant Chemotherapy in Patients Undergoing Complete Resection. J Clin Oncol 33:3439-46
Shepherd, Frances A; Domerg, Caroline; Hainaut, Pierre et al. (2013) Pooled analysis of the prognostic and predictive effects of KRAS mutation status and KRAS mutation subtype in early-stage resected non-small-cell lung cancer in four trials of adjuvant chemotherapy. J Clin Oncol 31:2173-81
Graziano, Stephen L; Lacas, Benjamin; Vollmer, Robin et al. (2013) Cross-validation analysis of the prognostic significance of mucin expression in patients with resected non-small cell lung cancer treated with adjuvant chemotherapy: results from IALT, JBR.10 and ANITA. Lung Cancer 82:149-55
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