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EGFR and K-Ras mutations in women with lung adenocarcinoma: implications for treatment strategy definition
BACKGROUND: We aimed at investigating the outcomes of female patients with stage IIIB-IV adenocarcinoma of the lung according to EGFR and K-Ras mutational status. METHODS: One hundred and three consecutive female patients genotyped at a single Italian Institution were analyzed. Patients were planned...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198726/ https://www.ncbi.nlm.nih.gov/pubmed/25300933 http://dx.doi.org/10.1186/s13046-014-0077-6 |
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author | Rotella, Virginia Fornaro, Lorenzo Vasile, Enrico Tibaldi, Carmelo Boldrini, Laura Chella, Antonio D’Incecco, Armida Cirigliano, Giovanna Chioni, Aldo Lupi, Cristiana Sensi, Elisa Ginocchi, Laura Giovannelli, Simona Pennucci, Maria Cristina Fontanini, Gabriella Baldini, Editta |
author_facet | Rotella, Virginia Fornaro, Lorenzo Vasile, Enrico Tibaldi, Carmelo Boldrini, Laura Chella, Antonio D’Incecco, Armida Cirigliano, Giovanna Chioni, Aldo Lupi, Cristiana Sensi, Elisa Ginocchi, Laura Giovannelli, Simona Pennucci, Maria Cristina Fontanini, Gabriella Baldini, Editta |
author_sort | Rotella, Virginia |
collection | PubMed |
description | BACKGROUND: We aimed at investigating the outcomes of female patients with stage IIIB-IV adenocarcinoma of the lung according to EGFR and K-Ras mutational status. METHODS: One hundred and three consecutive female patients genotyped at a single Italian Institution were analyzed. Patients were planned to receive first-line platinum-based chemotherapy (CT) and a salvage treatment with anti-EGFR tyrosine-kinase inhibitors (TKIs) was proposed irrespective of tumor mutational status. EGFR (exons 18–21) and K-Ras (exon 2, codons 12–13) mutations were evaluated by real-time PCR and pyrosequencing. The association of mutational status with clinical variables and treatment benefit was investigated by chi-square test and log-rank test. RESULTS: EGFR and K-Ras mutations were found in 31 (30%) and 13 (15%) cases, respectively. Sixty-six patients received platinum CT: no correlation was observed between EGFR or K-Ras mutational status and response rate (RR) (p > 0.05). However, patients treated with first-line CT harboring EGFR activating mutations experienced a significantly reduced progression-free survival (PFS) in comparison with wild-type ones (4.4 vs. 6.4 months, respectively; HR 0.597, 95% CI 0.287-0.975; p = 0.048). Thirty-nine patients received salvage treatment with erlotinib: EGFR activating mutations were significantly correlated with RR (60% vs. 12.5%; p = 0.004) and PFS (11.4 vs. 4.5 months; HR 0.491, 95% CI 0.216-0.936; p = 0.044). Responses to erlotinib were not reported among women with K-Ras mutant tumors, while 50% of those with wild-type K-Ras achieved an objective remission (p = 0.296). Median PFS (3.5 vs. 8.8 months; HR 0.284, 95% CI 0.015-0.510; p = 0.010) and OS (3.9 vs. 19.8 months; HR 0.158, 95% CI 0.001-0.075; p < 0.001) were significantly shorter among K-Ras mutant patients treated with TKI. CONCLUSIONS: In our population of Caucasian women with advanced lung adenocarcinoma we observed that the presence of EGFR activating mutations correlates with a significant reduction in the benefit from first-line platinum-based CT, emphasizing the importance of an upfront use of anti-EGFR TKIs in this patient subset. K-Ras mutations seem to correlate with a detrimental effect from anti-EGFR TKI, but this finding deserves further investigation. |
format | Online Article Text |
id | pubmed-4198726 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-41987262014-10-17 EGFR and K-Ras mutations in women with lung adenocarcinoma: implications for treatment strategy definition Rotella, Virginia Fornaro, Lorenzo Vasile, Enrico Tibaldi, Carmelo Boldrini, Laura Chella, Antonio D’Incecco, Armida Cirigliano, Giovanna Chioni, Aldo Lupi, Cristiana Sensi, Elisa Ginocchi, Laura Giovannelli, Simona Pennucci, Maria Cristina Fontanini, Gabriella Baldini, Editta J Exp Clin Cancer Res Research BACKGROUND: We aimed at investigating the outcomes of female patients with stage IIIB-IV adenocarcinoma of the lung according to EGFR and K-Ras mutational status. METHODS: One hundred and three consecutive female patients genotyped at a single Italian Institution were analyzed. Patients were planned to receive first-line platinum-based chemotherapy (CT) and a salvage treatment with anti-EGFR tyrosine-kinase inhibitors (TKIs) was proposed irrespective of tumor mutational status. EGFR (exons 18–21) and K-Ras (exon 2, codons 12–13) mutations were evaluated by real-time PCR and pyrosequencing. The association of mutational status with clinical variables and treatment benefit was investigated by chi-square test and log-rank test. RESULTS: EGFR and K-Ras mutations were found in 31 (30%) and 13 (15%) cases, respectively. Sixty-six patients received platinum CT: no correlation was observed between EGFR or K-Ras mutational status and response rate (RR) (p > 0.05). However, patients treated with first-line CT harboring EGFR activating mutations experienced a significantly reduced progression-free survival (PFS) in comparison with wild-type ones (4.4 vs. 6.4 months, respectively; HR 0.597, 95% CI 0.287-0.975; p = 0.048). Thirty-nine patients received salvage treatment with erlotinib: EGFR activating mutations were significantly correlated with RR (60% vs. 12.5%; p = 0.004) and PFS (11.4 vs. 4.5 months; HR 0.491, 95% CI 0.216-0.936; p = 0.044). Responses to erlotinib were not reported among women with K-Ras mutant tumors, while 50% of those with wild-type K-Ras achieved an objective remission (p = 0.296). Median PFS (3.5 vs. 8.8 months; HR 0.284, 95% CI 0.015-0.510; p = 0.010) and OS (3.9 vs. 19.8 months; HR 0.158, 95% CI 0.001-0.075; p < 0.001) were significantly shorter among K-Ras mutant patients treated with TKI. CONCLUSIONS: In our population of Caucasian women with advanced lung adenocarcinoma we observed that the presence of EGFR activating mutations correlates with a significant reduction in the benefit from first-line platinum-based CT, emphasizing the importance of an upfront use of anti-EGFR TKIs in this patient subset. K-Ras mutations seem to correlate with a detrimental effect from anti-EGFR TKI, but this finding deserves further investigation. BioMed Central 2014-10-11 /pmc/articles/PMC4198726/ /pubmed/25300933 http://dx.doi.org/10.1186/s13046-014-0077-6 Text en © Rotella et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Rotella, Virginia Fornaro, Lorenzo Vasile, Enrico Tibaldi, Carmelo Boldrini, Laura Chella, Antonio D’Incecco, Armida Cirigliano, Giovanna Chioni, Aldo Lupi, Cristiana Sensi, Elisa Ginocchi, Laura Giovannelli, Simona Pennucci, Maria Cristina Fontanini, Gabriella Baldini, Editta EGFR and K-Ras mutations in women with lung adenocarcinoma: implications for treatment strategy definition |
title | EGFR and K-Ras mutations in women with lung adenocarcinoma: implications for treatment strategy definition |
title_full | EGFR and K-Ras mutations in women with lung adenocarcinoma: implications for treatment strategy definition |
title_fullStr | EGFR and K-Ras mutations in women with lung adenocarcinoma: implications for treatment strategy definition |
title_full_unstemmed | EGFR and K-Ras mutations in women with lung adenocarcinoma: implications for treatment strategy definition |
title_short | EGFR and K-Ras mutations in women with lung adenocarcinoma: implications for treatment strategy definition |
title_sort | egfr and k-ras mutations in women with lung adenocarcinoma: implications for treatment strategy definition |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198726/ https://www.ncbi.nlm.nih.gov/pubmed/25300933 http://dx.doi.org/10.1186/s13046-014-0077-6 |
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