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.

Dadduzio, V., Basso, M., Rossi, S., Cenci, T., Capodimonti, S., Strippoli, A., Orlandi, A., Cerchiaro, E., Schinzari, G., Cassano, A., Martini, M., Barone, C. A., KRAS Exon 2 Mutations as Prognostic Indicators in Advanced Colorectal Cancer in Clinical Practice: A Mono-Institutional Study, <<MOLECULAR DIAGNOSIS & THERAPY>>, 2016; 20 (1): 65-74-74. [doi:10.1007/s40291-015-0178-8] [http://hdl.handle.net/10807/82698]

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

Dadduzio, Vincenzo
Primo
;
Basso, Michele
Secondo
;
Rossi, Sabrina;Cenci, Tonia;Capodimonti, Sara;Strippoli, Antonia;Orlandi, Armando;Cerchiaro, Eleonora;Schinzari, Giovanni;Cassano, Alessandra;Martini, Maurizio
Penultimo
;
Barone, Carlo Antonio
Ultimo
2016

Abstract

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.
Inglese
Dadduzio, V., Basso, M., Rossi, S., Cenci, T., Capodimonti, S., Strippoli, A., Orlandi, A., Cerchiaro, E., Schinzari, G., Cassano, A., Martini, M., Barone, C. A., KRAS Exon 2 Mutations as Prognostic Indicators in Advanced Colorectal Cancer in Clinical Practice: A Mono-Institutional Study, <<MOLECULAR DIAGNOSIS & THERAPY>>, 2016; 20 (1): 65-74-74. [doi:10.1007/s40291-015-0178-8] [http://hdl.handle.net/10807/82698]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/82698
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