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.
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.
Authors: W S Samowitz; K Curtin; D Schaffer; M Robertson; M Leppert; M L Slattery Journal: Cancer Epidemiol Biomarkers Prev Date: 2000-11 Impact factor: 4.254
Authors: C Bokemeyer; I Bondarenko; J T Hartmann; F de Braud; G Schuch; A Zubel; I Celik; M Schlichting; P Koralewski Journal: Ann Oncol Date: 2011-01-12 Impact factor: 32.976
Authors: Eric Van Cutsem; Claus-Henning Köhne; István Láng; Gunnar Folprecht; Marek P Nowacki; Stefano Cascinu; Igor Shchepotin; Joan Maurel; David Cunningham; Sabine Tejpar; Michael Schlichting; Angela Zubel; Ilhan Celik; Philippe Rougier; Fortunato Ciardiello Journal: J Clin Oncol Date: 2011-04-18 Impact factor: 44.544
Authors: Yu Imamura; Teppei Morikawa; Xiaoyun Liao; Paul Lochhead; Aya Kuchiba; Mai Yamauchi; Zhi Rong Qian; Reiko Nishihara; Jeffrey A Meyerhardt; Kevin M Haigis; Charles S Fuchs; Shuji Ogino Journal: Clin Cancer Res Date: 2012-07-02 Impact factor: 12.531
Authors: Eric Van Cutsem; Heinz-Josef Lenz; Claus-Henning Köhne; Volker Heinemann; Sabine Tejpar; Ivan Melezínek; Frank Beier; Christopher Stroh; Philippe Rougier; J Han van Krieken; Fortunato Ciardiello Journal: J Clin Oncol Date: 2015-01-20 Impact factor: 44.544
Authors: T Yokota; T Ura; N Shibata; D Takahari; K Shitara; M Nomura; C Kondo; A Mizota; S Utsunomiya; K Muro; Y Yatabe Journal: Br J Cancer Date: 2011-02-01 Impact factor: 7.640