Exploratory biomarker analysis for predicting treatment effects of aflibercept in the VELOUR trial.

• DOI: 10.1200/jco.2024.42.16_suppl.3592
• Publication Date: 2024-06-17T14:13:05Z
• Authors: Ting Pu; Allyson Peddle; Pratyaksha Wirapati; Yourae Hong; Leslie Samuel; Jayesh Desai; Maigo Riener; Zacharenia (Zenia...; David Cunningham; Sabine Tejpar; Petros Tsantoulis
• Keywords: Aflibercept; Exploratory analysis

3592 Background: Second-line treatment with aflibercept and FOLFIRI in patients metastatic colorectal carcinoma (mCRC) previously treated oxaliplatin improved overall survival (OS) versus placebo [Hazard ratio (HR), 0.81; 95% CI, 0.71–0.93; P=0.003] 1 . However, cancer (CRC) is a heterogenous disease the new intrinsic consensus molecular (iCMS) allows for tumours to be subtyped into unique genetic transcriptional features 2 We present post hoc analysis of VELOUR patient data, assess impact KRAS or BRAF mutation status iCMS on efficacy parameters. Methods: Patient samples were classified as either mutant wild-type (WT) via targeted panel Gene expression data was used classify iCMS2 iCMS3 using modified classifier based signatures which are specifically up-regulated tumour Results: Of 439 available RNA 54.9% (241/439) iCMS2; 45.1% (198/439) iCMS3; 48.3% (212/439) RAS 8.4% (37/439) RAF mutant. A favourable effect observed within WT group (Median OS from 11 17.7 months; HR 0.87; CI 0.79-0.96, P=0.005), particularly 15.5 30.4 0.70-0.94, P=0.004). This comparison where no benefit seen (HR 0.97; 0.82-1.14, P=0.683). In addition, (OS 1.03; 0.96-1.12, P=0.405). Progression-free (PFS) followed same trend. Aflibercept seemed also strongly 37 BRAF-mutated tumours, (PFS 0.46, 0.20-1.09; 0.65, 0.29-1.48), although differences not statistically significant. Irrespective treatment, 0.60; 0.48-0.75, P< 0.001) PFS 0.75; 0.60-0.94, P=0.011) all expected. Treatment-by-mutation interaction tests P=0.40, P=0.33) indicated that different among sub-groups, small sample size limited analysis. Conclusions: study, addition appears primarily especially those iCMS2. The prognostic but predictive response FOLFIRI. On contrary, provided numerical however P-values