The prognostic role of inflammatory markers in patients with metastatic colorectal cancer treated with bevacizumab: A translational study [ASCENT].
<h4>Background</h4>In spite of demonstrating prognostic and possibly predictive benefit in retrospective cohorts and meta-analyses of cancer populations, including colorectal cancer (CRC), prospective evaluation of the relationship between neutrophil to lymphocyte ratio (NLR) and treatme...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0229900 |
| _version_ | 1819093974481108992 |
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| author | Stephen John Clarke Matthew Burge Kynan Feeney Peter Gibbs Kristian Jones Gavin Marx Mark P Molloy Timothy Price William H H Reece Eva Segelov Niall C Tebbutt |
| author_facet | Stephen John Clarke Matthew Burge Kynan Feeney Peter Gibbs Kristian Jones Gavin Marx Mark P Molloy Timothy Price William H H Reece Eva Segelov Niall C Tebbutt |
| author_sort | Stephen John Clarke |
| collection | DOAJ |
| description | <h4>Background</h4>In spite of demonstrating prognostic and possibly predictive benefit in retrospective cohorts and meta-analyses of cancer populations, including colorectal cancer (CRC), prospective evaluation of the relationship between neutrophil to lymphocyte ratio (NLR) and treatment outcomes in previously untreated mCRC patients receiving bevacizumab-based therapy has not yet been performed.<h4>Methods</h4>An open-label, single arm, multi-centre study. Patients received first-line bevacizumab plus XELOX or mFOLFOX6 (Phase-A) and continued bevacizumab plus FOLFIRI beyond first progression (Phase-B). Analyses included the association of NLR with phase A progression free survival (PFS) and overall survival (OS). A sub-study investigated the safety in patients with the primary in situ tumor. An exploratory sub-study examined relationships of circulating proteomic markers with PFS.<h4>Results</h4>Phase-A enrolled 128 patients; median age was 64 years (range: 26-84), 70 (55%) were female, 71 (56%) were PS-0 and 51 (40%) had primary in situ tumor. Fifty-three (41%) patients entered Phase-B. The median baseline (b) NLR was 3.2 (range: 1.5-20.4) with 32 (25%) patients having bNLR > 5. The PFS hazard ratio (HR) by bNLR > 5 versus ≤ 5 was 1.4 (95% CI: 0.9-2.2; p = 0.101). The median PFS was 9.2 months (95% CI: 7.9-10.8) for Phase-A and 6.7 months (95% CI: 3.0-8.2) for Phase-B. The HR for OS based on bNLR > 5 versus ≤ 5 was 1.6 (95% CI: 1.0-2.7; p = 0.052). The median OS was 25 months (95% CI: 19.2-29.7) for the full analysis set and 14.9 months for Phase-B. Baseline levels of nine proteomic markers showed a relationship with PFS. Treatment related toxicities were consistent with what has previously been published. There were 4 (3%) instances of GI perforation, of which, 3 (6%) occurred in the primary in situ tumor group.<h4>Conclusions</h4>Results from this study are aligned with the previously reported trend towards worse PFS and OS in patients with higher bNLR.<h4>Trial registration</h4>ClinicalTrials.gov: NCT01588990; posted May 1, 2012. |
| first_indexed | 2024-12-21T23:20:02Z |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T23:20:02Z |
| publishDate | 2020-01-01 |
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| spelling | doaj.art-cd2703a957b846b1ba3c1198c841daa42022-12-21T18:46:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01153e022990010.1371/journal.pone.0229900The prognostic role of inflammatory markers in patients with metastatic colorectal cancer treated with bevacizumab: A translational study [ASCENT].Stephen John ClarkeMatthew BurgeKynan FeeneyPeter GibbsKristian JonesGavin MarxMark P MolloyTimothy PriceWilliam H H ReeceEva SegelovNiall C Tebbutt<h4>Background</h4>In spite of demonstrating prognostic and possibly predictive benefit in retrospective cohorts and meta-analyses of cancer populations, including colorectal cancer (CRC), prospective evaluation of the relationship between neutrophil to lymphocyte ratio (NLR) and treatment outcomes in previously untreated mCRC patients receiving bevacizumab-based therapy has not yet been performed.<h4>Methods</h4>An open-label, single arm, multi-centre study. Patients received first-line bevacizumab plus XELOX or mFOLFOX6 (Phase-A) and continued bevacizumab plus FOLFIRI beyond first progression (Phase-B). Analyses included the association of NLR with phase A progression free survival (PFS) and overall survival (OS). A sub-study investigated the safety in patients with the primary in situ tumor. An exploratory sub-study examined relationships of circulating proteomic markers with PFS.<h4>Results</h4>Phase-A enrolled 128 patients; median age was 64 years (range: 26-84), 70 (55%) were female, 71 (56%) were PS-0 and 51 (40%) had primary in situ tumor. Fifty-three (41%) patients entered Phase-B. The median baseline (b) NLR was 3.2 (range: 1.5-20.4) with 32 (25%) patients having bNLR > 5. The PFS hazard ratio (HR) by bNLR > 5 versus ≤ 5 was 1.4 (95% CI: 0.9-2.2; p = 0.101). The median PFS was 9.2 months (95% CI: 7.9-10.8) for Phase-A and 6.7 months (95% CI: 3.0-8.2) for Phase-B. The HR for OS based on bNLR > 5 versus ≤ 5 was 1.6 (95% CI: 1.0-2.7; p = 0.052). The median OS was 25 months (95% CI: 19.2-29.7) for the full analysis set and 14.9 months for Phase-B. Baseline levels of nine proteomic markers showed a relationship with PFS. Treatment related toxicities were consistent with what has previously been published. There were 4 (3%) instances of GI perforation, of which, 3 (6%) occurred in the primary in situ tumor group.<h4>Conclusions</h4>Results from this study are aligned with the previously reported trend towards worse PFS and OS in patients with higher bNLR.<h4>Trial registration</h4>ClinicalTrials.gov: NCT01588990; posted May 1, 2012.https://doi.org/10.1371/journal.pone.0229900 |
| spellingShingle | Stephen John Clarke Matthew Burge Kynan Feeney Peter Gibbs Kristian Jones Gavin Marx Mark P Molloy Timothy Price William H H Reece Eva Segelov Niall C Tebbutt The prognostic role of inflammatory markers in patients with metastatic colorectal cancer treated with bevacizumab: A translational study [ASCENT]. PLoS ONE |
| title | The prognostic role of inflammatory markers in patients with metastatic colorectal cancer treated with bevacizumab: A translational study [ASCENT]. |
| title_full | The prognostic role of inflammatory markers in patients with metastatic colorectal cancer treated with bevacizumab: A translational study [ASCENT]. |
| title_fullStr | The prognostic role of inflammatory markers in patients with metastatic colorectal cancer treated with bevacizumab: A translational study [ASCENT]. |
| title_full_unstemmed | The prognostic role of inflammatory markers in patients with metastatic colorectal cancer treated with bevacizumab: A translational study [ASCENT]. |
| title_short | The prognostic role of inflammatory markers in patients with metastatic colorectal cancer treated with bevacizumab: A translational study [ASCENT]. |
| title_sort | prognostic role of inflammatory markers in patients with metastatic colorectal cancer treated with bevacizumab a translational study ascent |
| url | https://doi.org/10.1371/journal.pone.0229900 |
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