Predictive role of multiple gene alterations in response to cetuximab in metastatic colorectal cancer: a single center study.

Journal of Translational Medicine
Paola UliviAlessandro Passardi

Abstract

KRAS mutations negatively affect outcome after treatment with cetuximab in metastatic colorectal cancer (mCRC) patients. As only 20% of KRAS wild type (WT) patients respond to cetuximab it is possible that other mutations, constitutively activating the EGFR pathway, are present in the non-responding KRAS WT patients. We retrospectively analyzed objective tumor response rate, (ORR) progression-free (PFS) and overall survival (OS) with respect to the mutational status of KRAS, BRAF, PIK3CA and PTEN expression in mCRC patients treated with a cetuximab-based regimen. 67 mCRC patients were enrolled onto the study. DNA was extracted from paraffin-embedded sections derived from primary or metastatic lesions. Exon 2 of KRAS and exon 15 of BRAF were analyzed by direct sequencing, PIK3CA was evaluated by pyrosequencing and PTEN expression by immunohistochemistry. BRAF and PIK3CA mutations were independently associated with worse PFS (p = 0.006 and p = 0.028, respectively) and OS (p = 0.008 and p = 0.029, respectively). No differences in clinical outcome were found between patients who were positive or negative for PTEN expression. Conversely, patients negative for KRAS, BRAF and PIK3CA mutations were characterized by significantly better...Continue Reading

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Mar 20, 2014·PloS One·Andrea Casadei GardiniGiovanni Luca Frassineti
Feb 7, 2014·Cancer Chemotherapy and Pharmacology·Tomokazu KishikiMasanori Sugiyama
Aug 16, 2014·PloS One·Andrea MafficiniAldo Scarpa
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Mar 21, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Eric Van CutsemJosep Tabernero
Oct 12, 2019·Visceral Medicine·Thomas SeufferleinThomas J Ettrich

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Methods Mentioned

BETA
PCR
electrophoresis

Software Mentioned

SAS

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