Abstract
BackgroundThe use of bevacizumab in combination with fluoropyrimidine-containing chemotherapy is a well-established first-line and second-line treatment for patients with metastatic colorectal cancer (mCRC). However, there remains a need for reproducible, validated, inexpensive and accessible prognostic markers to aid treatment selection. The optimal treatment duration and the role of bevacizumab in certain patient subgroups, considered at particular risk of bevacizumab-mediated toxicity, also require further investigation. The aim of the ASCENT study [an Australian translational Study to evaluate the prognostic role of inflammatory markers in patients with metastatic ColorEctal caNcer Treated with bevacizumab (Avastin™)] is to evaluate the relationship between the host inflammatory response as measured by neutrophil/lymphocyte ratio (NLR) and treatment outcomes in patients with previously untreated mCRC receiving bevacizumab-based first- and second-line treatment.Methods/designThis open-label, prospective, single arm, phase IV, Australian multi-centre study evaluates the relationship between the host inflammatory response as measured by NLR and treatment outcomes in patients with previously untreated mCRC receiving bevacizumab-based first- and second-line treatment. 150 patients will be recruited from 16 centres around Australia. Patients will receive trial treatments in two phases: Phase A: XELOX or mFOLFOX6 plus bevacizumab administered from study start until first disease progression; and Phase B: FOLFIRI plus bevacizumab administered from first disease progression until second disease progression. The primary analysis will test the association between NLR and progression free survival using a proportional Hazards Model. Secondary analyses will investigate whether the relationship can be improved upon with other prognostic biomarkers, and further characterise the safety of bevacizumab following treatment initiation, and when continued after progression in combination with standard chemotherapy regimens (presented through summary statistics and Kaplan Meier curves).DiscussionQuantifying the relationship between NLR and PFS will inform decision making on the extent to which this simple metric may be applied clinically.Trial registrationClinicalTrials.gov: NCT01588990
Highlights
The use of bevacizumab in combination with fluoropyrimidine-containing chemotherapy is a wellestablished first-line and second-line treatment for patients with metastatic colorectal cancer
The trial consists of two phases of treatment: Phase A treatment: Oral capecitabine plus infusional oxaliplatin (XELOX) or mFOLFOX6 plus bevacizumab administered from study start until first disease progression; Phase B treatment: Infusional 5-fluoarouracil (FOLFIRI) plus bevacizumab administered from first disease progression until second disease progression
To date there is no validated or reproducible prognostic biomarker to assist clinicians with determining the most likely treatment outcomes for patients with metastatic colorectal cancer (mCRC) treated with bevacizumab-containing regimens
Summary
The use of bevacizumab in combination with fluoropyrimidine-containing chemotherapy is a wellestablished first-line and second-line treatment for patients with metastatic colorectal cancer (mCRC). The aim of the ASCENT study [an Australian translational Study to evaluate the prognostic role of inflammatory markers in patients with metastatic ColorEctal caNcer Treated with bevacizumab (AvastinTM)] is to evaluate the relationship between the host inflammatory response as measured by neutrophil/lymphocyte ratio (NLR) and treatment outcomes in patients with previously untreated mCRC receiving bevacizumab-based first- and second-line treatment. Combination chemotherapy with fluoropyrimidine/oxaliplatin (FOLFOX or XELOX) or 5-FU/LV/irinotecan (FOLFIRI) provides higher response rates, longer progression-free survival (PFS) and better overall survival (OS) than a fluoropyrimidine alone Both FOLFOX/XELOX and FOLFIRI have similar efficacy regardless of the sequence used but have different toxicity profiles [5]. Favorable survival has been shown to correlate with the percentage of patients receiving all active chemotherapeutic agents, emphasizing the importance of exposure to all active drugs during treatment [6]
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