EGFR related mutational status and association to clinical outcome of third-line cetuximab-irinotecan in metastatic colorectal cancer
<p>Abstract</p> <p>Background</p> <p>As supplement to <it>KRAS </it>mutational analysis<it>, BRAF and PIK3CA </it>mutations as well as expression of PTEN may account for additional non-responders to anti-EGFR-MoAbs treatment. The aim of the prese...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2011-03-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | http://www.biomedcentral.com/1471-2407/11/107 |
| _version_ | 1811277857077329920 |
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| author | Frifeldt Sanne K Lindebjerg Jan Pallisgaard Niels Spindler Karen-Lise G Jakobsen Anders |
| author_facet | Frifeldt Sanne K Lindebjerg Jan Pallisgaard Niels Spindler Karen-Lise G Jakobsen Anders |
| author_sort | Frifeldt Sanne K |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>As supplement to <it>KRAS </it>mutational analysis<it>, BRAF and PIK3CA </it>mutations as well as expression of PTEN may account for additional non-responders to anti-EGFR-MoAbs treatment. The aim of the present study was to investigate the utility as biomarkers of these mutations in a uniform cohort of patients with metastatic colorectal cancer treated with third-line cetuximab/irinotecan.</p> <p>Methods</p> <p>One-hundred-and-seven patients were prospectively included in the study. Mutational analyses of <it>KRAS, BRAF </it>and <it>PIK3CA </it>were performed on DNA from confirmed malignant tissue using commercially available kits. Loss of PTEN and EGFR was assessed by immunohistochemistry.</p> <p>Results</p> <p>DNA was available in 94 patients. The frequency of KRAS, <it>BRAF </it>and <it>PIK3CA </it>mutations were 44%, 3% and 14%, respectively. All were non-responders. EGF receptor status by IHC and loss of PTEN failed to show any clinical importance. <it>KRAS </it>and <it>BRAF </it>were mutually exclusive. Supplementing <it>KRAS </it>analysis with <it>BRAF </it>and <it>PIK3CA </it>indentified additional 11% of non-responders. Patient with any mutation had a high risk of early progression, whereas triple-negative status implied a response rate (RR) of 41% (p < 0.001), a disease control (DC) rate of 73% (p < 001), and a significantly higher PFS of 7.7(5.1-8.6 95%CI) versus 2.3 months (2.1-3.695%CI) (p < 0.000).</p> <p>Conclusion</p> <p>Triple-negative status implied a clear benefit from treatment, and we suggest that patient selection for third-line combination therapy with cetuximab/irinotecan could be based on triple mutational testing.</p> |
| first_indexed | 2024-04-13T00:24:10Z |
| format | Article |
| id | doaj.art-24750d2d77494bf69671c51a65d83786 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-13T00:24:10Z |
| publishDate | 2011-03-01 |
| publisher | BMC |
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| series | BMC Cancer |
| spelling | doaj.art-24750d2d77494bf69671c51a65d837862022-12-22T03:10:39ZengBMCBMC Cancer1471-24072011-03-0111110710.1186/1471-2407-11-107EGFR related mutational status and association to clinical outcome of third-line cetuximab-irinotecan in metastatic colorectal cancerFrifeldt Sanne KLindebjerg JanPallisgaard NielsSpindler Karen-Lise GJakobsen Anders<p>Abstract</p> <p>Background</p> <p>As supplement to <it>KRAS </it>mutational analysis<it>, BRAF and PIK3CA </it>mutations as well as expression of PTEN may account for additional non-responders to anti-EGFR-MoAbs treatment. The aim of the present study was to investigate the utility as biomarkers of these mutations in a uniform cohort of patients with metastatic colorectal cancer treated with third-line cetuximab/irinotecan.</p> <p>Methods</p> <p>One-hundred-and-seven patients were prospectively included in the study. Mutational analyses of <it>KRAS, BRAF </it>and <it>PIK3CA </it>were performed on DNA from confirmed malignant tissue using commercially available kits. Loss of PTEN and EGFR was assessed by immunohistochemistry.</p> <p>Results</p> <p>DNA was available in 94 patients. The frequency of KRAS, <it>BRAF </it>and <it>PIK3CA </it>mutations were 44%, 3% and 14%, respectively. All were non-responders. EGF receptor status by IHC and loss of PTEN failed to show any clinical importance. <it>KRAS </it>and <it>BRAF </it>were mutually exclusive. Supplementing <it>KRAS </it>analysis with <it>BRAF </it>and <it>PIK3CA </it>indentified additional 11% of non-responders. Patient with any mutation had a high risk of early progression, whereas triple-negative status implied a response rate (RR) of 41% (p < 0.001), a disease control (DC) rate of 73% (p < 001), and a significantly higher PFS of 7.7(5.1-8.6 95%CI) versus 2.3 months (2.1-3.695%CI) (p < 0.000).</p> <p>Conclusion</p> <p>Triple-negative status implied a clear benefit from treatment, and we suggest that patient selection for third-line combination therapy with cetuximab/irinotecan could be based on triple mutational testing.</p>http://www.biomedcentral.com/1471-2407/11/107metastatic colorectal cancerKRASBRAFPIK3CA/PTEN mutationsCetuximab and Irinotecan |
| spellingShingle | Frifeldt Sanne K Lindebjerg Jan Pallisgaard Niels Spindler Karen-Lise G Jakobsen Anders EGFR related mutational status and association to clinical outcome of third-line cetuximab-irinotecan in metastatic colorectal cancer BMC Cancer metastatic colorectal cancer KRAS BRAF PIK3CA/PTEN mutations Cetuximab and Irinotecan |
| title | EGFR related mutational status and association to clinical outcome of third-line cetuximab-irinotecan in metastatic colorectal cancer |
| title_full | EGFR related mutational status and association to clinical outcome of third-line cetuximab-irinotecan in metastatic colorectal cancer |
| title_fullStr | EGFR related mutational status and association to clinical outcome of third-line cetuximab-irinotecan in metastatic colorectal cancer |
| title_full_unstemmed | EGFR related mutational status and association to clinical outcome of third-line cetuximab-irinotecan in metastatic colorectal cancer |
| title_short | EGFR related mutational status and association to clinical outcome of third-line cetuximab-irinotecan in metastatic colorectal cancer |
| title_sort | egfr related mutational status and association to clinical outcome of third line cetuximab irinotecan in metastatic colorectal cancer |
| topic | metastatic colorectal cancer KRAS BRAF PIK3CA/PTEN mutations Cetuximab and Irinotecan |
| url | http://www.biomedcentral.com/1471-2407/11/107 |
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