Integrating tissue and liquid biopsy comprehensive genomic profiling to predict efficacy of anti-EGFR therapies in metastatic colorectal cancer: Findings from the CAPRI-2 GOIM study

Introduction: We investigated the role of integrating tissue biopsy (TBx)- and liquid biopsy (LBx)-comprehensive genomic profiling (CGP) to predict the activity of FOLFIRI plus cetuximab. Methods: The CAPRI-2 GOIM study is a non-randomized phase 2 study evaluating a biomarker-driven anti-EGFR treatment in three lines of therapy in patients with RAS/BRAFV600E wild type metastatic colorectal cancer. At baseline, TBx and LBx were analyzed using the FoundationOne CDx platform. Analysis of overall response rate (ORR) and median progression free survival (mPFS) according to molecular profiles were performed. Results: Overall, 156 patients were evaluable for tumor response and had matched tissue and plasma-based CGP. Negatively hyper-selected patients by both TBx- and LBx-CGP showed higher ORR (79.6 % versus 44.2 %, P < 0.001) and mPFS compared to mutated cases (12.4 months versus 7.4 months, P < 0.001). Eight and 12 cases harbored mutations detected by TBx and LBx-CGP only, respectively. Compared to discordant cases (n = 20), concordant cases (n = 23) showed a trend for lower ORR (39.1 % versus 50.0 %, P = 0.5) and shorter mPFS (3.94 versus 11.50 months, P = 0.02). Patients with alterations detected only by TBx-CGP had significantly lower circulating tumor DNA (ctDNA) tumor fraction (TF) compared to concordant cases (1.7 % versus 23.0 %; P = 0.01). Using a ctDNA TF threshold ≥ 10 % nearly all (19 of 20) TBx detected pathogenic variants (PV) were also identified by LBx-CGP. In eight cases detected by LBx only, mPFS was 8.24 months. Conclusion: In cases with high TF LBx-CGP predicts efficacy of anti-EGFR therapy, while for TF< 10 % TBx-CGP provides additional data on PVs that could affect treatment efficacy.