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Ann Oncol. 2014 Sep;25(9):1756-61. doi: 10.1093/annonc/mdu230. Epub 2014 Jun 18.

Clinical activity of FOLFIRI plus cetuximab according to extended gene mutation status by next-generation sequencing: findings from the CAPRI-GOIM trial.

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  • 1Department of Clinical and Experimental Medicine 'F. Magrassi', Medical Oncology, Second University of Naples, Naples
  • 2Cell Biology and Biotherapy Unit, National Cancer Institute 'Fondazione Giovanni Pascale', Naples.
  • 3Medical Oncology, Hospital Casa Sollievo Della Sofferenza-San Giovanni Rotondo (Foggia), San Giovanni Rotondo.
  • 4Department of Clinical and Experimental Medicine 'F. Magrassi', Medical Oncology, Second University of Naples, Naples.
  • 5Department of Medical Oncology, Hospital SS. Annunziata, Taranto.
  • 6Department of Medical Oncology, National Cancer Institute Giovanni Paolo II, Bari.
  • 7Department of Medical Oncology, University Hospital A. Gemelli, Rome.
  • 8Department of Medical Oncology, Hospital 'A. Cardarelli', Naples.
  • 9Department of Medical Oncology, Hospital Monaldi- Azienda Ospedaliera dei Colli, Napoles.
  • 10Department of Medical Oncology, Univeristy Hospital Campus Bio-Medico di Rome, Rome.
  • 11Department of Medical Oncology, Hospital A. Perrino, Brindisi.
  • 12Department of Medical Oncology, Hospital Garibaldi, Nesima, Catania.
  • 13Department of Medical Oncology, Hospital Sacro Cuore di Gesù, Fatebenefratelli, Benevento.
  • 14Department of Medical Oncology, Hospital Polo Occidentale, Castellaneta, Bari.
  • 15Department of Pathology, National Cancer Institute 'Fondazione Giovanni Pascale', Naples, Italy.



Treatment with antiepidermal growth factor receptor (anti-EGFR) monoclonal antibodies has been restricted to metastatic colorectal cancer (mCRC) patients with RAS wild-type tumors. Next-generation sequencing (NGS) allows the assessment in a single analysis of a large number of gene alterations and might provide important predictive and prognostic information.


In the CAPRI-GOIM trial, 340 KRAS exon 2 wild-type mCRC patients received first-line FOLFIRI plus cetuximab. Tumor samples (182/340, 53.5%) were assessed by NGS to search for mutations in 22 genes involved in colon cancer.


Objective responses in the NGS cohort were observed in 104/182 patients [overall response rate (ORR) 57.1%; 95% confidence interval (95% CI) 52% to 66.4%] with a median progression-free survival (mPFS) of 9.8 (95% CI 8.7-11.5) months. NGS analysis was successfully completed in all 182 samples. One or more gene mutations (up to five) were detected in 124/182 (68.1%) tumors within 14/22 genes for a total of 206 mutations. KRAS exon 2 mutations were identified in 29/182 (15.9%) samples, defined as wild type by local laboratory assessment. Frequently mutated genes were: TP53 (39.6%), KRAS exons 3/4 (8.8%), NRAS exons 2/3 (7.1%), PIK3CA exons 9/20 (13.2%), BRAF (8.2%). FOLFIRI plus cetuximab treatment determined ORR of 62.0% (95% CI 55.5% to 74.6%) with mPFS of 11.1 (95% CI 9.2-12.8) months in patients with KRAS and NRAS wild-type tumors. Conversely, ORR was 46.6% (95% CI 39.9-57.5%) with mPFS of 8.9 (95% CI 7.4-9.6) months in patients with KRAS or NRAS mutations. Similarly, the subgroup of patients carrying KRAS, NRAS, BRAF, or PIK3CA mutations showed a worse outcome, although this might be due to a prognostic effect.


This study demonstrates that NGS analysis in mCRC is feasible, reveals high level of intra and intertumor heterogeneity, and identifies patients that might benefit of FOLFIRI plus cetuximab treatment.

© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email:


BRAF; KSA/NRAS; PIK3CA; cetuximab; colorectal cancer; next-generation sequencing

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