Dynamic angiogenic switch as predictor of response to chemotherapy+ bevacizumab in patients with metastatic colorectal cancer.

Abstract

Listen

Translate article

e15126 Background: There is a need to develop biomarkers to predict the outcome of patients with metastatic colorectal cancer (CRC) treated with chemotherapy (Ch) plus Bevacizumab (B). It has been reported that during exposure to B there is a switch in the plasma levels of angiogenesis growth factors and related cytokines called angiogenic switch (AS). It is not known if variations in AS among patients is related to the response to treatment with angiogenesis inhibitors. This study aimed to determine the influence of AS in the PFS of patients with metastatic colorectal cancer treated with Ch + B. Methods: Patients with untreated metastatic colorectal cancer with ECOG 0-1 performance status 0-1 were eligible. Patients received treatment with standard dose capecitabine plus either oxaliplatin or irinotecan and bevacizumab for six cycles either followed by maintenance treatment with bevacizumab plus capecitabine until progression. Angiogenic related cytokines (HGF, PIGF, MCP-3, MM-9, Eotaxin, bFGF and IL-18) were prospectively analyzed at baseline and every eight weeks). AS + was defined by A) doubling of PIGF compared to baseline or B) PIGF elevation with a simultaneous elevation of any two of bFGF, HGF, MCP-3, IL-18 or MMP-9 compared to baseline Results: Of 71 patients, 41 (57.8%) progressed with a median PFS of 10,1 (95% CI: 8.3 to 13,7) months. Forty-five (63.4%) patients developed an AS including 28 patients were AS + observed at first evaluation. Thirty five, six, and four patients were deemed AS + based on both criteria, criteria A or B respectively.. Median PFS for the 45 patients with AS was 11,4 (95% CI:8,6 to 15,8) months versus 8.3 (95% CI: 5.6 to 16.4) months in the 26 AS - patients (p = 0.04). The overall disease control rate (PR + CR + stable disease in AS + patients was 96% versus 58 % in AS – patients (p < 0.001). Conclusions: Development of AS is associated with better PFS and disease control in patients with metastatic CRC treated with bevacizumab in combination with chemotherapy. These data support continuing studying dynamic changes in circulating angiogenic factors and cytokines as markers of angiogenesis inhibitors effectiveness. Clinical trial information: NCT02075086.