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Worse prognosis of KRAS c.35 G > A mutant metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx)

BACKGROUND: Prognosis of KRAS wild-type and mutant metastatic colorectal cancer (MCRC) patients (pts) treated with bevacizumab (BEV)-containing chemotherapy is not significantly different. Since specific KRAS mutations confer different aggressive behaviors, the prognostic role of prevalent KRAS muta...

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Autores principales: Bruera, Gemma, Cannita, Katia, Di Giacomo, Daniela, Lamy, Aude, Frébourg, Thierry, Sabourin, Jean Christophe, Tosi, Mario, Alesse, Edoardo, Ficorella, Corrado, Ricevuto, Enrico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3635869/
https://www.ncbi.nlm.nih.gov/pubmed/23497191
http://dx.doi.org/10.1186/1741-7015-11-59
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author Bruera, Gemma
Cannita, Katia
Di Giacomo, Daniela
Lamy, Aude
Frébourg, Thierry
Sabourin, Jean Christophe
Tosi, Mario
Alesse, Edoardo
Ficorella, Corrado
Ricevuto, Enrico
author_facet Bruera, Gemma
Cannita, Katia
Di Giacomo, Daniela
Lamy, Aude
Frébourg, Thierry
Sabourin, Jean Christophe
Tosi, Mario
Alesse, Edoardo
Ficorella, Corrado
Ricevuto, Enrico
author_sort Bruera, Gemma
collection PubMed
description BACKGROUND: Prognosis of KRAS wild-type and mutant metastatic colorectal cancer (MCRC) patients (pts) treated with bevacizumab (BEV)-containing chemotherapy is not significantly different. Since specific KRAS mutations confer different aggressive behaviors, the prognostic role of prevalent KRAS mutations was retrospectively evaluated in MCRC pts treated with first line FIr-B/FOx, associating BEV to triplet chemotherapy. METHODS: Tumor samples were screened for KRAS codon 12, 13 and BRAF V600E mutations by SNaPshot and/or direct sequencing. MCRC pts <75-years-old were consecutively treated with FIr-B/FOx: weekly 12 hour-timed-flat-infusion/5-fluorouracil (900 mg/m(2 )on days 1,2, 8, 9, 15, 16,22, 23), irinotecan plus BEV (160 mg/m(2 )and 5 mg/kg, respectively, on days 1,15); and oxaliplatin (80 mg/m(2), on days 8,22). Pts were classified as liver-limited (L-L) and other/multiple metastatic (O/MM). Progression-free survival (PFS) and overall survival (OS) were compared using the log-rank test. RESULTS: Fifty-nine pts were evaluated at a median follow-up of 21.5 months. KRAS mutant pts: c.35 G > A, 15 (25.4%); c.35 G > T, 7 (11.8%); c.38 G > A, 3 (5%); other, 3 (5%). KRAS wild-type, 31 pts (52.7%). The objective response rate (ORR), PFS and OS were, respectively: c.35 G > A mutant, 71%, 9 months, 14 months; other than c.35 G > A mutants, 61%, 12 months, 39 months. OS was significantly worse in c.35 G > A pts compared to KRAS wild-type (P = 0.002), KRAS/BRAF wild-type (P = 0.03), other MCRC patients (P = 0.002), other than c.35 G > A (P = 0.05), other codon 12 (P = 0.03) mutant pts. OS was not significantly different compared to c.35 G > T KRAS mutant (P = 0.142). CONCLUSIONS: KRAS c.35 G > A mutant status may be significantly associated with a worse prognosis of MCRC pts treated with first line FIr-B/FOx intensive regimen compared to KRAS/BRAF wild type and other than c.35 G > A mutant pts.
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spelling pubmed-36358692013-04-26 Worse prognosis of KRAS c.35 G > A mutant metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx) Bruera, Gemma Cannita, Katia Di Giacomo, Daniela Lamy, Aude Frébourg, Thierry Sabourin, Jean Christophe Tosi, Mario Alesse, Edoardo Ficorella, Corrado Ricevuto, Enrico BMC Med Research Article BACKGROUND: Prognosis of KRAS wild-type and mutant metastatic colorectal cancer (MCRC) patients (pts) treated with bevacizumab (BEV)-containing chemotherapy is not significantly different. Since specific KRAS mutations confer different aggressive behaviors, the prognostic role of prevalent KRAS mutations was retrospectively evaluated in MCRC pts treated with first line FIr-B/FOx, associating BEV to triplet chemotherapy. METHODS: Tumor samples were screened for KRAS codon 12, 13 and BRAF V600E mutations by SNaPshot and/or direct sequencing. MCRC pts <75-years-old were consecutively treated with FIr-B/FOx: weekly 12 hour-timed-flat-infusion/5-fluorouracil (900 mg/m(2 )on days 1,2, 8, 9, 15, 16,22, 23), irinotecan plus BEV (160 mg/m(2 )and 5 mg/kg, respectively, on days 1,15); and oxaliplatin (80 mg/m(2), on days 8,22). Pts were classified as liver-limited (L-L) and other/multiple metastatic (O/MM). Progression-free survival (PFS) and overall survival (OS) were compared using the log-rank test. RESULTS: Fifty-nine pts were evaluated at a median follow-up of 21.5 months. KRAS mutant pts: c.35 G > A, 15 (25.4%); c.35 G > T, 7 (11.8%); c.38 G > A, 3 (5%); other, 3 (5%). KRAS wild-type, 31 pts (52.7%). The objective response rate (ORR), PFS and OS were, respectively: c.35 G > A mutant, 71%, 9 months, 14 months; other than c.35 G > A mutants, 61%, 12 months, 39 months. OS was significantly worse in c.35 G > A pts compared to KRAS wild-type (P = 0.002), KRAS/BRAF wild-type (P = 0.03), other MCRC patients (P = 0.002), other than c.35 G > A (P = 0.05), other codon 12 (P = 0.03) mutant pts. OS was not significantly different compared to c.35 G > T KRAS mutant (P = 0.142). CONCLUSIONS: KRAS c.35 G > A mutant status may be significantly associated with a worse prognosis of MCRC pts treated with first line FIr-B/FOx intensive regimen compared to KRAS/BRAF wild type and other than c.35 G > A mutant pts. BioMed Central 2013-03-04 /pmc/articles/PMC3635869/ /pubmed/23497191 http://dx.doi.org/10.1186/1741-7015-11-59 Text en Copyright © 2013 Bruera et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Bruera, Gemma
Cannita, Katia
Di Giacomo, Daniela
Lamy, Aude
Frébourg, Thierry
Sabourin, Jean Christophe
Tosi, Mario
Alesse, Edoardo
Ficorella, Corrado
Ricevuto, Enrico
Worse prognosis of KRAS c.35 G > A mutant metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx)
title Worse prognosis of KRAS c.35 G > A mutant metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx)
title_full Worse prognosis of KRAS c.35 G > A mutant metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx)
title_fullStr Worse prognosis of KRAS c.35 G > A mutant metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx)
title_full_unstemmed Worse prognosis of KRAS c.35 G > A mutant metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx)
title_short Worse prognosis of KRAS c.35 G > A mutant metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx)
title_sort worse prognosis of kras c.35 g > a mutant metastatic colorectal cancer (mcrc) patients treated with intensive triplet chemotherapy plus bevacizumab (fir-b/fox)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3635869/
https://www.ncbi.nlm.nih.gov/pubmed/23497191
http://dx.doi.org/10.1186/1741-7015-11-59
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