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KRAS Mutations Predict Response and Outcome in Advanced Lung Adenocarcinoma Patients Receiving First-Line Bevacizumab and Platinum-Based Chemotherapy

Bevacizumab, combined with platinum-based chemotherapy, has been widely used in the treatment of advanced-stage lung adenocarcinoma (LADC). Although KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutation is the most common genetic alteration in human LADC and its role in promoting angi...

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Autores principales: Ghimessy, Áron Kristof, Gellert, Áron, Schlegl, Erzsebet, Hegedus, Balazs, Raso, Erzsebet, Barbai, Tamas, Timar, Jozsef, Ostoros, Gyula, Megyesfalvi, Zsolt, Gieszer, Balazs, Moldvay, Judit, Renyi-Vamos, Ferenc, Lohinai, Zoltan, Hoda, Mir Alireza, Klikovits, Thomas, Klepetko, Walter, Laszlo, Viktoria, Dome, Balazs
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827133/
https://www.ncbi.nlm.nih.gov/pubmed/31600989
http://dx.doi.org/10.3390/cancers11101514
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author Ghimessy, Áron Kristof
Gellert, Áron
Schlegl, Erzsebet
Hegedus, Balazs
Raso, Erzsebet
Barbai, Tamas
Timar, Jozsef
Ostoros, Gyula
Megyesfalvi, Zsolt
Gieszer, Balazs
Moldvay, Judit
Renyi-Vamos, Ferenc
Lohinai, Zoltan
Hoda, Mir Alireza
Klikovits, Thomas
Klepetko, Walter
Laszlo, Viktoria
Dome, Balazs
author_facet Ghimessy, Áron Kristof
Gellert, Áron
Schlegl, Erzsebet
Hegedus, Balazs
Raso, Erzsebet
Barbai, Tamas
Timar, Jozsef
Ostoros, Gyula
Megyesfalvi, Zsolt
Gieszer, Balazs
Moldvay, Judit
Renyi-Vamos, Ferenc
Lohinai, Zoltan
Hoda, Mir Alireza
Klikovits, Thomas
Klepetko, Walter
Laszlo, Viktoria
Dome, Balazs
author_sort Ghimessy, Áron Kristof
collection PubMed
description Bevacizumab, combined with platinum-based chemotherapy, has been widely used in the treatment of advanced-stage lung adenocarcinoma (LADC). Although KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutation is the most common genetic alteration in human LADC and its role in promoting angiogenesis has been well established, its prognostic and predictive role in the above setting remains unclear. The association between KRAS exon 2 mutational status and clinicopathological variables including progression-free survival and overall survival (PFS and OS, respectively) was retrospectively analyzed in 501 Caucasian stage IIIB-IV LADC patients receiving first-line platinum-based chemotherapy (CHT) with or without bevacizumab (BEV). EGFR (epidermal growth factor receptor)-mutant cases were excluded. Of 247 BEV/CHT and 254 CHT patients, 95 (38.5%) and 75 (29.5%) had mutations in KRAS, respectively. KRAS mutation was associated with smoking (p = 0.008) and female gender (p = 0.002) in the BEV/CHT group. We found no difference in OS between patients with KRAS-mutant versus KRAS wild-type tumors in the CHT-alone group (p = 0.6771). Notably, patients with KRAS-mutant tumors demonstrated significantly shorter PFS (p = 0.0255) and OS (p = 0.0186) in response to BEV/CHT compared to KRAS wild-type patients. KRAS mutation was an independent predictor of shorter PFS (hazard ratio, 0.597; p = 0.011) and OS (hazard ratio, 0.645; p = 0.012) in the BEV/CHT group. G12D KRAS-mutant patients receiving BEV/CHT showed significantly shorter PFS (3.7 months versus 8.27 months in the G12/13x group; p = 0.0032) and OS (7.2 months versus 16.1 months in the G12/13x group; p = 0.0144). In this single-center, retrospective study, KRAS-mutant LADC patients receiving BEV/CHT treatment exhibited inferior PFS and OS compared to those with KRAS wild-type advanced LADC. G12D mutations may define a subset of KRAS-mutant LADC patients unsuitable for antiangiogenic therapy with BEV.
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spelling pubmed-68271332019-11-18 KRAS Mutations Predict Response and Outcome in Advanced Lung Adenocarcinoma Patients Receiving First-Line Bevacizumab and Platinum-Based Chemotherapy Ghimessy, Áron Kristof Gellert, Áron Schlegl, Erzsebet Hegedus, Balazs Raso, Erzsebet Barbai, Tamas Timar, Jozsef Ostoros, Gyula Megyesfalvi, Zsolt Gieszer, Balazs Moldvay, Judit Renyi-Vamos, Ferenc Lohinai, Zoltan Hoda, Mir Alireza Klikovits, Thomas Klepetko, Walter Laszlo, Viktoria Dome, Balazs Cancers (Basel) Article Bevacizumab, combined with platinum-based chemotherapy, has been widely used in the treatment of advanced-stage lung adenocarcinoma (LADC). Although KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutation is the most common genetic alteration in human LADC and its role in promoting angiogenesis has been well established, its prognostic and predictive role in the above setting remains unclear. The association between KRAS exon 2 mutational status and clinicopathological variables including progression-free survival and overall survival (PFS and OS, respectively) was retrospectively analyzed in 501 Caucasian stage IIIB-IV LADC patients receiving first-line platinum-based chemotherapy (CHT) with or without bevacizumab (BEV). EGFR (epidermal growth factor receptor)-mutant cases were excluded. Of 247 BEV/CHT and 254 CHT patients, 95 (38.5%) and 75 (29.5%) had mutations in KRAS, respectively. KRAS mutation was associated with smoking (p = 0.008) and female gender (p = 0.002) in the BEV/CHT group. We found no difference in OS between patients with KRAS-mutant versus KRAS wild-type tumors in the CHT-alone group (p = 0.6771). Notably, patients with KRAS-mutant tumors demonstrated significantly shorter PFS (p = 0.0255) and OS (p = 0.0186) in response to BEV/CHT compared to KRAS wild-type patients. KRAS mutation was an independent predictor of shorter PFS (hazard ratio, 0.597; p = 0.011) and OS (hazard ratio, 0.645; p = 0.012) in the BEV/CHT group. G12D KRAS-mutant patients receiving BEV/CHT showed significantly shorter PFS (3.7 months versus 8.27 months in the G12/13x group; p = 0.0032) and OS (7.2 months versus 16.1 months in the G12/13x group; p = 0.0144). In this single-center, retrospective study, KRAS-mutant LADC patients receiving BEV/CHT treatment exhibited inferior PFS and OS compared to those with KRAS wild-type advanced LADC. G12D mutations may define a subset of KRAS-mutant LADC patients unsuitable for antiangiogenic therapy with BEV. MDPI 2019-10-09 /pmc/articles/PMC6827133/ /pubmed/31600989 http://dx.doi.org/10.3390/cancers11101514 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ghimessy, Áron Kristof
Gellert, Áron
Schlegl, Erzsebet
Hegedus, Balazs
Raso, Erzsebet
Barbai, Tamas
Timar, Jozsef
Ostoros, Gyula
Megyesfalvi, Zsolt
Gieszer, Balazs
Moldvay, Judit
Renyi-Vamos, Ferenc
Lohinai, Zoltan
Hoda, Mir Alireza
Klikovits, Thomas
Klepetko, Walter
Laszlo, Viktoria
Dome, Balazs
KRAS Mutations Predict Response and Outcome in Advanced Lung Adenocarcinoma Patients Receiving First-Line Bevacizumab and Platinum-Based Chemotherapy
title KRAS Mutations Predict Response and Outcome in Advanced Lung Adenocarcinoma Patients Receiving First-Line Bevacizumab and Platinum-Based Chemotherapy
title_full KRAS Mutations Predict Response and Outcome in Advanced Lung Adenocarcinoma Patients Receiving First-Line Bevacizumab and Platinum-Based Chemotherapy
title_fullStr KRAS Mutations Predict Response and Outcome in Advanced Lung Adenocarcinoma Patients Receiving First-Line Bevacizumab and Platinum-Based Chemotherapy
title_full_unstemmed KRAS Mutations Predict Response and Outcome in Advanced Lung Adenocarcinoma Patients Receiving First-Line Bevacizumab and Platinum-Based Chemotherapy
title_short KRAS Mutations Predict Response and Outcome in Advanced Lung Adenocarcinoma Patients Receiving First-Line Bevacizumab and Platinum-Based Chemotherapy
title_sort kras mutations predict response and outcome in advanced lung adenocarcinoma patients receiving first-line bevacizumab and platinum-based chemotherapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827133/
https://www.ncbi.nlm.nih.gov/pubmed/31600989
http://dx.doi.org/10.3390/cancers11101514
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