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Title: The prognostic role of inflammatory markers in patients with metastatic colorectal cancer treated with bevacizumab: A translational study [ASCENT].
Austin Authors: Clarke, Stephen John;Burge, Matthew;Feeney, Kynan;Gibbs, Peter;Jones, Kristian;Marx, Gavin;Molloy, Mark P;Price, Timothy;Reece, William H H;Segelov, Eva;Tebbutt, Niall C 
Affiliation: Biostatistics, Covance Pty Ltd, Sydney, Australia
Cancer Services, Royal North Shore Hospital, St Leonards, Australia
Department of Medical Oncology, Austin Health, Heidelberg, Victoria, Australia
Medical Oncology, St Vincent's Hospital, Darlinghurst, Australia
Haematology and Medical Oncology, The Queen Elizabeth Hospital and University of Adelaide, Adelaide, Australia
Australian Proteome Analysis Facility, Macquarie University, Sydney, Australia
Integrated Cancer Centre, Sydney Adventist Hospital, and University of Sydney, Wahroonga, Australia
Medical Affairs, Roche Products, Pty, Limited, Sydney, Australia
Medical Oncology, Western Hospital, Footscray, Australia
Department of Oncology, Haematology and Palliative Care, St John of God Murdoch Hospital, Murdoch, Australia
Cancer Care Services, Royal Brisbane and Women Hospital, and University of Queensland, Herston, Australia
Issue Date: 2020 2020
Publication information: PLoS One 2020; 15(3): e0229900
Abstract: 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. 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. 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. Results from this study are aligned with the previously reported trend towards worse PFS and OS in patients with higher bNLR. NCT01588990; posted May 1, 2012.
DOI: 10.1371/journal.pone.0229900
ORCID: 0000-0001-5817-1222
PubMed URL: 32142532
Type: Journal Article
Appears in Collections:Journal articles

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