The prognostic role of inflammatory markers in patients with metastatic colorectal cancer treated with bevacizumab: A translational study [ASCENT].

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

Results from this study are aligned with the previously reported trend towards worse PFS and OS in patients with higher bNLR.

TRIAL REGISTRATION

ClinicalTrials.gov: NCT01588990; posted May 1, 2012.

Déclaration de conflit d'intérêts

SC has served on advisory boards for Roche Products, Pty. Limited and has received travel support. MB has served on advisory boards for Roche Products, Pty. Limited and has received travel support. KF has served on advisory boards for Roche Products, Pty. Limited and has received travel support. PG has served on advisory boards for Roche Products, Pty. Limited, has received consultancy fees, travel and research support. MM is an employee of Macquarie University who was contracted by Roche Products, Pty. Limited for proteomic analyses. GM declared no conflict of interest. TP has served on advisory boards for Roche Products, Pty. Limited and has received travel support. ES has served on advisory boards for Roche Products, Pty. Limited and has received travel support. NT has served on Advisory Boards for Roche Products, Pty. Limited and has received travel support. KJ is an employee of Roche Products, Pty. Limited (the study sponsor). WR is an employee of Covance Pty. Ltd who was contracted by Roche Products, Pty. Limited. This does not alter our adherence to PLOS ONE policies on sharing data and materials.