1655P - High mRNA expression of LMO4, a BRCA1 downregulator, correlates with better prognosis in erlotinib-treated non-small-cell lung cancer (NSCLC) patien...

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Non-Small-Cell Lung Cancer, Metastatic
Translational Research
Presenter Niki Karachaliou
Authors N. Karachaliou1, C. Costa2, A. Gimenez-Capitan2, S. Viteri1, A. Gasco1, C. Camps3, E. Carcereny4, B. Massuti Sureda5, J. Souglakos6, R. Rosell4
  • 1Oncology, Instituto Oncologico Dr Rosell, USP Dexeus University Institute, 08028 - Barcelona/ES
  • 2Laboratoy Of Biology Department, Pangaea Biotech, USP Dexeus University Institute, 08028 - Barcelona/ES
  • 3Oncology, Hospital General de Valencia, 46014 - Valencia/ES
  • 4Medical Oncology Service, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, 08916 - Badalona/ES
  • 5Medical Oncology, Hospital General Universitario de Alicante, ES-03010 - Alicante/ES
  • 6Oncology, University Hospital of Heraklion, 71110 - Crete/GR

Abstract

Background

High BRCA1 mRNA levels affected progression-free survival (PFS) to erlotinib in EGFR-mutant NSCLC p (Rosell et al. CCR 2011). LMO4 is a negative regulator of BRCA1 function, and CtIP can bind to BRCA1 and LMO4. We have assessed the expression of CtIP, LMO4 and BRCA1 and examined the impact of CtIP and LMO4 levels on outcome.

Methods

mRNA expression of BRCA1, LMO4 and CtIP was examined by RT-PCR in the original pretreatment tumor biopsies of 72 erlotinb-treated NSCLC p with sensitive EGFR mutations.

Results

p characteristics: median age, 68; 61.8% female; 98.2% Caucasian; 63.6% never-smokers; 81.8% ECOG PS < 2; 95 adenocarcinoma; 94.5% stage IV. BRCA1 expression correlated with that of CtIP (&rgr; = 0.31; P = 0.01) and LMO4 (&rgr; = 0.32; P = 0.02). PFS for p with high LMO4 levels was not reached while it was 13 months (m) for p with low levels (P = 0.006). Overall survival (OS) was not reached for p with high levels of LMO4 and was 31 m for p with low levels (P = 0.17). PFS was not reached for p with low BRCA1 and high LMO4 levels and was 19 m for p with low levels of both genes (P = 0.04). PFS was 8 m for p with high BRCA1 and low LMO4 levels and 18 m for p with high levels of both genes (P = 0.03). In the multivariate analysis, BRCA1 and LMO4 expression emerged as markers of PFS (Table).

Conclusions

Low BRCA1 and high LMO4 levels were associated with longer PFS in erlotinib-treated advanced NSCLC p with EGFR mutations. We recommend baseline assessment of BRCA1 and LMO4 mRNA expression to predict outcome and provide alternative individualized treatment to patients when indicated.

HR 95%CI P
BRCA1
≤4.92 1 ref.
4.92-10.7 5.32 1.45-19.52 0.03
>10.7 5.13 1.25-20.99 0.02
CtIP
≤1.21 1 ref.
1.21-2.1 0.69 0.24-2.02 0.50
>2.1 1.10 0.42-2.89 0.84
LMO4
≤1.29 6.02 1.51-23.94 0.01
1.29-1.86 2.81 0.85-9.21 0.09
>1.86 1 ref.

Disclosure

All authors have declared no conflicts of interest.