KRAS Exon 2 Mutations as Prognostic Indicators in Advanced Colorectal Cancer in Clinical Practice: A Mono-Institutional Study.

Background: Kirsten-Ras ( KRAS) mutations are widely accepted negative predictive factors for anti- EGFR therapies in metastatic colorectal cancer (mCRC), while their prognostic significance is still under discussion. Objective: This mono-institutional retrospective study aims to investigate the real-life impact of exon 2 codon 12 and 13 mutations in mCRC. Methods: All mCRC patients treated at our institution between 2008 and 2014 carrying KRAS exon 2 mutations were included. The primary endpoint was to determine any significant difference in overall survival (OS) between codon 12 and 13 mutations. Secondary endpoints included progression-free survival (PFS), OS in both populations according to antiangiogenic treatment, and OS in liver-limited disease (LLD). Results: Of 620 mCRC patients, 218 carried KRAS exon 2 mutations (35.1 %): 162 (26.1 %) at codon 12 and 56 (9.0 %) at codon 13. Median OS results were similar: 32.0 months (codon 12) and 31.0 months (codon 13). PFS was also comparable, reaching 10.8 months in both populations. The addition of bevacizumab to chemotherapy conferred a trend toward survival advantage in codon 12 but not codon 13 mutation ( p = 0.058). A high proportion of LLD patients underwent hepatic surgery with radical purpose (62.3 %): in these patients, median OS has not yet been reached, while OS in non-LLD patients was 30.2 months. Conclusions: No difference in OS between KRAS codon 12/13 mutated disease was found. This analysis showed a very prolonged OS for KRAS-mutated patients, even when LLD patients were excluded; OS of our real-life series favorably compares with OS of all- RAS wild-type patients in recent randomized studies. [ABSTRACT FROM AUTHOR]