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1243P IDENTIFICATION OF MICRORNA (MIRNA) SIGNATURES FOR
RESPONSE AND SURVIVAL IN NON-SMALL CELL LUNG
CANCER (NSCLC) PATIENTS (PTS) TREATED WITH
CISPLATIN-VINORELBINE (CV): A ELCWP STUDY
I. Cstoth 1 , T. Berghmans 1 , L. Willems 2 , M. Paesmans 3 , L. Ameye 3 , J. Lafitte 4 ,
A. Scherpereel 4 , A. Cortot 4 , C. Mascaux 1 , J. Sculier 5
1 Thoracic Oncology, Institut Jules Bordet, Brussels, BELGIUM, 2 Molecular and
Cellular Biology Laboratory, Gemboux Agro-Bio Tech, Gembloux, BELGIUM,
3 Data Centre, Institute Jules Bordet, Brussels, BELGIUM, 4 Pneumology, CHU
Lille, Lille, FRANCE, 5 Intensive Care and Thoracic Oncology, Institut Jules
Bordet, Brussels, BELGIUM
Background: Clinical variables, like stage and performance status (PS), have
predictive and prognostic values in advanced NSCLC pts treated with chemotherapy,
but not on an individual basis. As a secondary aim of a prospective study, we
assessed the predictive (for response) and prognostic (for survival) values of miRNA
expression in NSCLC pts treated by C (60 mg/m 2 D1) and V (25 mg/m 2 , D1 + 8) in
1 st line chemotherapy.
Methods: During the diagnostic bronchoscopy, a tumour biopsy was lysed into
Tripure Isolation Reagent (Roche Diagnostics) on ice, snap frozen and stored at -80°
C. miRNA expression was assessed using TaqMan Low Density Arrays (756 human
miR panel, Applied Biosystems) and normalized using the delta delta CT method to
RNU48 (SNORD48) CT value for every sample. Survival was measured from the
registration date and response by WHO criteria.
Results: From 180 pts screened between 04/2009 and 11/2011, 38 pts were eligible
including 27 males, 26 pts with Karnofsky PS of 80-100, 20 adenocarcinomas and 30
stage IV. Sixteen partial responses (43%) were observed. After stepwise selection, a
two miRNA (miR-149 and miR-375) predictive signature for response to CV (AUC
0.90, sensitivity 88%, negative predictive value 89%) which was related to
progression-free survival (medians 12 and 17 months (ms), respectively, p = 0.047).
Using a linear combination of the miRNA CT values with Cox’s regression
coefficients as weights, a prognostic score for survival including 4 miRNA (miR-200c,
miR-424, miR-29c and miR-124) was identified. The signature distinguished pts with
good (n = 18) and poor (n = 20) prognosis with median survival of 47.3 months
(95% CI 29.8-52.4) and 15.5 months (95% CI 9.1-22.8), respectively (p C SNP, 3R G > C SNP) and
methylenetetrahydrofolate reductase (MTHFR) (C677T, A1298C). Progression-free
survival (PFS) and overall survival (OS) were evaluated according to each genotype.
Results: 103 patients with stage III-IV NSCLC (47% adenocarcinoma, 41%
squamous cell carcinoma, 12% NOS) receiving platinum-based chemotherapy were
eligible (14 patients with stage I-II were excluded). The median PFS was significantly
longer in patients with C/T or T/T genotypes in codon 118 in ERCC1: 13 months
(m) and 10 m, respectively, as compared to 6 m for the C/C patients (p = 0.034).
Patients with ERCC1 C/T or T/T genotypes had a trend to longer median OS (20 m)
than those C/C (10.5 m; p = 0.1). Subgroup analysis revealed that ERCC1 C/T or T/T
genotypes were associated with increased PFS in male (p = 0.005), smokers (p =
Annals of Oncology
0.036) and age