Impact of STAT3 Phosphorylation on the Clinical Effectiveness of Anti-EGFR–Based Therapy in Patients With Metastatic Colorectal Cancer

Abstract

BackgroundSignal transducer and activator of transcription 3 (STAT3) is involved in epithelial growth factor receptor (EGFR) signaling in a KRAS-independent manner. Phosphorylated STAT3 (pSTAT3) expression in patients with metastatic colorectal cancer (mCRC) treated with anti-EGFR–containing salvage chemotherapy has never been investigated. Patients and Methods:The first endpoint of this retrospective study was to evaluate the impact of pSTAT3 on the time to progression (TTP) in 94 patients with mCRC treated with anti-EGFR–based therapies in the second- or third-line setting between July 2004 and November 2009. The influence of pSTAT3 on objective response rate and overall survival (OS) was also reported. Nuclear expression of pSTAT3 status was evaluated by immunohistochemical tests on formalin-fixed and paraffin-embedded tumor samples obtained before therapy. ResultsPositive expression of pSTAT3 was observed in 24.5% of the tumor samples. The probability of achieving an objective response was 13% among patients with positive nuclear expression of pSTAT3 compared with 41% for patients displaying pSTAT3-negative tumors (P = .02). In a multivariate logistic regression model, high-grade skin rash, wild-type KRAS status, and negative pSTAT3 status significantly improved TTP and OS. ConclusionThese results underscore an impact of pSTAT3 on the clinical efficacy of anti-EGFR–containing chemotherapy regimens and support the prospective assessment of this biomarker.