535P - MIR-99A/LET7C/MIR-125B signature to predict sensitivity to anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC)

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Colon Cancer
Rectal Cancer
Translational Research
Presenter Federico Cappuzzo
Authors F. Cappuzzo1, A. Sacconi2, L. Landi3, F. Biagioni2, V. Ludovini4, E. Sensi5, J. Salvini3, G. Fontanini5, G. Blandino2, L. Crinò6
  • 1U.o. Oncologia Medica, Istituto Toscano Tumori, 57124 - Livorno/IT
  • 2Oncology, Istituto Nazionale Tumori Regina Elena, Roma/IT
  • 3Oncology, Istituto Toscano Tumori, Livorno/IT
  • 4Medical Oncology Division, S. Maria della Misericordia Hospital,, 06132 - Perugia/IT
  • 5Pathology, Azienda Ospedaliera Universitaria Pisana, Pisa/IT
  • 6Department Of Medical Oncology, Perugia Hospital, 06156 - Perugia/IT

Abstract

Background

MicroRNAs (MiRNAs) are a class of non-coding RNAs that bind to complementary sequences on target messenger RNA transcripts, causing either degradation or inhibition of translation, silencing their mRNA target. Available data indicated that MiRNA levels could modulate sensitivity to targeted agents, including anti-EGFR compounds. In the present study we aimed to investigate whether MiRNA signature was predictive for sensitivity to anti-EGFR monoclonal antibodies in mCRC.

Methods

A total of 183 mCRC from two independent cohorts (cohort 1: 74 cases; validation cohort: 109 cases) treated with cetuximab/panitumumab either alone (N = 19) or in combination with chemotherapy (N = 164) were included onto the study. MiRNA arrays were analysed using Agilent's miRNA platform.

Results

MiRNA array analyses identified the cluster miR-99a/Let7c/miR-125b located on 21p11.1 as associated with different outcome to anti-EGFR therapies. In the first cohort, patients with high signature (N = 25, 33,8%) had a significantly longer progression free survival (PFS, 6.1 versus 2.3 months, p = 0.02, HR = 0.42) and overall survival (OS, 29.8 versus 7.0 months, p = 0.08, HR = 0.39) than patients with low signature (N = 23, 31,1%). Similar results were observed in the validation cohort. Patients with high signature (N = 37, 33,9%) had a significantly longer PFS and longer OS than individuals with low signature (N = 35, 32.1%; PFS 7.8 versus 4.3 months, p = 0.02, HR = 0.56; OS 12.8 versus 7.5 months, p = 0.02, HR = 0.65). To further assess the potential confounding effect of KRAS and BRAF mutations, we analyzed the outcome of patients with high and low signature in the 75 cases with KRAS or BRAF mutation and in 98 cases KRAS and BRAF wild-type. In the wild-type population, high signature patients (N = 31, 31.6%) had a significantly longer PFS (8,2 versus 4.4 months, p = 0.02, HR:0,54) and longer OS (16,9 versus 10.9 months, p = 0.1, HR = 0,68) than low signature individuals, with no difference in the KRAS or BRAF mutated patients.

Conclusions

MiR-99a/Let7c/miR-125b signature is useful for improving selection of KRAS/BRAF wild-type mCRC patients candidate for anti-EGFR strategies.

Disclosure

All authors have declared no conflicts of interest.