The Impact of Concordance Between Liquid and Tissue Biopsy for Actionable Mutations: Insights from the Rome Trial

Purpose: This analysis evaluated the influence of tissue and liquid biopsy concordance on outcomes in patients enrolled in the ROME Trial. Experimental design: The ROME trial, a phase II multicenter study, enrolled 1,794 patients with advanced solid tumors. Next-generation sequencing (NGS) was performed on tissue and liquid biopsies using FoundationOne CDx and FoundationOne Liquid CDx, A centralized Molecular Tumor Board (MTB) reviewed results to identify actionable alterations, with 400 patients randomized to tailored therapy (TT) or standard-of-care (SoC).TT improved objective response rate and progression-free survival (PFS) in the Intention to Treat population. Concordance was defined as the detection of the same druggable alteration in both biopsy types; discordance indicated detection in only one. Results: Concordance was present in 49% of cases, with alterations detected exclusively in tissue (35%) or liquid (16%) biopsies. Patients in the concordant group receiving TT experienced improved survival outcomes. Median overall survival (OS) was 11.05 vs. 7.70 months in the SoC group (HR 0.74; 95% CI: 0.51-1.07), and median PFS was 4.93 vs. 2.80 months (HR 0.55; 95% CI: 0.40-0.76). In contrast, the survival benefit of TT was less pronounced or absent in patients with discordant results. OS was higher in the T+L group (11.05 months), followed by tissue-only (9.93 months), and liquid-only groups (4.05months). PFS followed a similar pattern, with the longest PFS in T+L group (4.93 months) vs 3.06 months in tissue-only and 2.07 months in liquid-only groups. Conclusions: The study highlights the potential value of integrating both biopsy modalities in selected clinical contexts.