1243P - Identification of microrna (miRNA) signatures for response and survival in non-small cell lung cancer (NSCLC) patients (pts) treated with cisplatin-...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Non-Small-Cell Lung Cancer, Metastatic
Translational Research
Presenter Ingrid Cstoth
Authors I. Cstoth1, T. Berghmans2, L. Willems3, M. Paesmans4, L. Ameye4, J. Lafitte5, A. Scherpereel5, A. Cortot5, C. Mascaux1, J. Sculier6
  • 1Thoracic Oncology, Institut Jules Bordet, 1000 - Brussels/BE
  • 2Institut Jules Bordet, 1000 - Brussels/BE
  • 3Molecular And Cellular Biology Laboratory, Gemboux Agro-Bio Tech, 5030 - Gembloux/BE
  • 4Data Centre, Institute Jules Bordet, BE-1000 - Brussels/BE
  • 5Pneumology, CHU Lille, Lille/FR
  • 6Intensive Care And Thoracic Oncology, Institut Jules Bordet, 1000 - Brussels/BE

Abstract

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/m2 D1) and V (25 mg/m2, D1 + 8) in 1st 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 <0.001; hazard ratio 21.1, 95% CI 4.7-94.9).

Conclusions

miRNA signatures are predictive of response and are prognostic for survival in patients with NSCLC treated with cisplatin-vinorelbine in 1st line. The validation of these results in an independent cohort, taking in consideration conventional prognostic factors, is ongoing.

Disclosure

All authors have declared no conflicts of interest.