HEPATIC FLEXTURE OF COLON TRIAL

A subgroup analysis of the AIO KRK-0306 trial revealed similar findings in patients with expanded RAS wild-type CRC. Recently, clinical studies have shown that a left-sided primary tumor site was associated with the benefits of cetuximab, which is one of the anti-EGFR antibodies, in patients with KRAS wild-type (exon 2 nonmutant) CRC. Left- and right-sided CRC (LCRC and RCRC) have different clinicopathological and molecular characteristics. The negative predictive roles of expanded RAS have been well established, but other biomarkers, including BRAF V600E mutation, amplification of KRAS, MET, and ERBB2, and cross-talk with PI3K/Akt/PETN, still remain to be investigational. Besides, the primary resistance mechanisms of cetuximab have been investigated rigorously. Some predictive biomarkers, such as the gene expression of EGFR ligands, have been reported to correlate with patient responses after the anti-EGFR antibody treatment. These studies have emphasized the importance of additional predictive biomarkers for anti-EGFR antibody treatment. However, not all patients experienced clinical benefits of the anti-EGFR antibody treatment. Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR), either used alone, or a combination with cytotoxic agents have been demonstrated to prolong survival in patients with metastatic colorectal cancer (CRC) harboring KRAS wild-type or expanded RAS. Our findings demonstrate that a left-sided primary tumor site is a useful predictor of improved cetuximab efficacy in the third-line or salvage treatment of KRAS wild-type (exon 2 nonmutant) metastatic CRC. Multivariate analysis revealed a right-sided primary tumor site was an independent predictor of shorter TTD (adjusted hazard ratio = 1.32, using the LCRC group as a reference, 95 % confidence interval: 1.08–1.61, P = .0072) and OS (adjusted HR = 1.45, 95 % CI: 1.18–1.78, P = .0003). 8.07 months, P < .0001) after the start of cetuximab treatment. Patients with LCRC, compared to patients with RCRC, had longer TTD (median, 4.59 vs. Among them, 765 (78.9 %) and 136 (14.0 %) patients had LCRC and RCRC, respectively. ResultsĪ total of 969 CRC patients were enrolled. Time to treatment discontinuation (TTD) and overall survival (OS) after the start of cetuximab treatment were compared between patients with LCRC (splenic flexure to rectum) and RCRC (cecum to hepatic flexure). Survival data were obtained from the National Death Registry. This study enrolled a cohort of patients, who had received cetuximab treatment after two or more lines of chemotherapy for KRAS wild-type (exon 2 nonmutant) metastatic CRC, from the databases of Taiwan Cancer Registry (2004–2010) and National Health Insurance (2004–2011). We explored the association between the primary tumor site and cetuximab efficacy in KRAS wild-type colorectal cancer (CRC). Previous studies have shown left-sided colorectal cancer (LCRC) and right-sided colorectal cancer (RCRC) exhibit different molecular and clinicopathological features.

Hepatic flexture of colon