Profiling plasma angiogenesis factors after use of biologics in metastatic colorectal cancer (mCRC): Update results from GI-SCREEN CRC Ukit study.

Abstract

3529 Background: No predictive biomarkers have been validated to determine which patients (pts) with metastatic colorectal cancer (mCRC) benefit the most from angiogenesis inhibitors. Recent studies suggest that plasma angiogenesis factors and their dynamics may have some prognostic or predictive value. Methods: In this prospective longitudinal study, serial plasma sample collections were done at the time points of pre- and post-treatments in mCRC pts receiving biologics in either first- or second-line chemotherapy (chemo). Comprehensive measurements of 17 factors were performed by the multiplex assay with Luminex technology. Statistical analyses were conducted by using the Brunner-Munzel and Jonckheere-Terpstra test. Results: From Sep 2017 to Dec 2020, 789 plasma samples were collected from 498 enrolled pts [first-line chemo plus bevacizumab (BEV, n=102), first-line chemo plus anti-EGFR antibody (aEGFR, n=100), second-line chemo plus BEV (n=100), second-line FOLFIRI plus ramucirumab (RAM, n=99), second-line FOLFIRI plus aflibercept (AFL, n=85) and other treatment (n=7)]. 789 samples were evaluable for this analysis. In the analysis of first-line, level of VEGF-D was significantly higher in both post-BEV and post-aEGFR comparing with pre-first-line [pre-first-line; 264 pg/ml, post-first-line BEV; 354 pg/ml (p<0.001), post-first-line aEGFR; 380.5 pg/ml (p<0.001)], while PlGF was significantly higher only in post-BEV [pre-first-line; 6.7 pg/ml, post-first-line BEV; 23.4 pg/ml (p<0.001), post-first-line EGFR; 7.4 pg/ml (p=0.650)]. These dynamics were also observed in pts with paired samples (Table). In pts with paired samples who received second-line treatment, level of VEGF-A was significantly decreased in post-BEV, while it significantly increased in post-RAM and AFL. A significant elevation of VEGF-D level was observed in only post-RAM. PlGF level significantly increased in post all second-line angiogenesis inhibitors. In the distribution analysis of angiogenesis factors, there were no or weak correlations between VEGF-D and PlGF at the time points of all post-treatments (r = 0.09-0.26). Conclusions: Plasma levels of VEGF-D, VEGF-A and PlGF were independently changed by angiogenesis inhibitors as well as anti-EGFR therapy, suggesting the possibility of usefulness for selecting better biologics by measuring baseline angiogenesis-related factors in first- and second-line chemo. Clinical trial information: UMIN000028616. [Table: see text]