349P Analysis of plasma angiogenesis factors on the efficacy of 2nd-line (2L) chemotherapy (chemo) combined with angiogenesis inhibitors (AIs) in metastatic colorectal cancer (mCRC): Results from GI-SCREEN CRC Ukit study

Abstract

Angiogenesis factors have been reported as prognostic and predictive biomarkers of AIs for mCRC, but its significance as a predictor of efficacy in 2L chemo combined with AIs has not been established. In 295 enrolled patients (pts) with mCRC receiving chemo plus AI in 2L treatment from Sep 2017 to Dec 2020, serial plasma samples were prospectively collected at the time points of pre- and post-treatment. 17 plasma angiogenesis factors were analyzed by the multiplex assay with Luminex technology. Interactions of their pre-treatment measurements with treatment groups on PFS were assessed via Cox proportional hazards model. The strength of interactions was examined using estimated generalized propensity score as weight, and the continuous plasma angiogenesis variables were dichotomized according to the median. The significance level for the interaction was defined as two-sided p ≤0.1. 283 pts were included in adjusted 2L cohort (chemo plus bevacizumab [BEV [reference]: n=100], FOLFIRI plus ramucirumab [RAM: n=98], FOLFIRI plus aflibercept [AFL: n=85]). Baseline characteristics in this cohort were as follows; median age 67 years; male 57.2%; left-sided tumor 70.3%; RAS mutant 50.2%; prior BEV 72.8%. Propensity-score weighted Cox model for PFS compared RAM with BEV showed significant interactions in HGF (median 174 pg/mL, High: HR 1.278, Low: HR 0.737, interaction p = 0.0485), sVEGFR-1 (median 985 pg/mL, High: HR 0.692, Low: HR 1.419, interaction p = 0.0106), and sVEGFR-3 (median 17200 pg/mL, High: HR 0.658, Low: HR 1.396, interaction p = 0.0065). On the other hand, there were no significant interactions for PFS compared AFL with BEV.Table: 349PBelow medianAbove medianInteraction p-value∗BEVRAMBEVRAMBelow vs above medianHGF6.9 m6.7 m4.0 m2.1 m0.0485sVEGFR-16.2 m3.9 m5.9 m5.8 m0.0106sVEGFR-36.4 m3.7 m5.7 m6.7 m0.0065Median PFS, ∗defined as p ≤0.1 Open table in a new tab Pre-treatment plasma HGF, sVEGFR-1 and sVEGFR-3 could be biomarkers that contribute to the optimal regimen selection of FOLFIRI plus RAM or chemo+BEV in 2L treatment of mCRC.