Abstract 6372: Combined tissue and liquid biopsy improves outcomes in advanced solid tumors: an exploratory analysis of the ROME trial
Authors: Paolo Marchetti, Simone Scagnoli, Edoardo Crimini, Simona Pisegna, Sofia Verkhovskaia, Giuseppe Curigliano, Sara Lonardi, Valentina Guarneri, Chiara Cremolini, Umberto Malapelle, Ettore D. Capoluongo, Paolo A. Ascierto, Fabio Puglisi, Giancarlo Pruneri, Giulia D'Amati, Bruna Cerbelli, Mauro Biffoni, Giuseppe Tonini, Lucia Del Mastro, Andrea Botticelli
Journal: Cancer Research (2025)

Abstract Background: The ROME trial, a phase II multicenter study, enrolled 1,794 patients with advanced solid tumors. Centralized next-generation sequencing (NGS) was performed on both 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 subsequently randomized to tailored therapy (TT) or standard-of-care (SoC). In this trial, TT improved objective response rate (ORR) and progression-free survival (PFS) in the Intention to Treat population (ITT) Methods: This exploratory analysis evaluated the concordance between tissue (T) and liquid (L) biopsy results in detecting actionable alterations in ITT population. Concordance was defined as the detection of the same significant alterations in both biopsy types; discordance indicated detection in only one. Survival outcomes (OS and PFS) were analyzed across concordance groups. Due to the exploratory nature of the analysis, statistical significance was not determined Results: Concordance between tissue (T) and liquid (L) biopsies was 49%, with actionable alterations detected exclusively in tissue biopsies in 35% of patients and exclusively in liquid biopsies in 16%. Of the 203 discordant cases, 21% were attributed to test failures, 35% to discordant high tumor mutational burden (hTMB) detection, 1% to microsatellite instability (MSI) discrepancies, and 43.3% to differences in the detection of molecular alterations. The PI3K/PTEN/AKT/mTOR and ERBB2 pathways showed the highest discordance rates. Test results guided therapeutic choices in 84% and 65% of cases for tissue biopsy and liquid biopsy, respectively. Patients in the concordant T+L group receiving tailored therapy (TT) experienced significantly improved survival outcomes. Median overall survival (OS) was 11.05 vs. 7.70 months in the standard-of-care (SoC) group (HR 0.74; 95% CI: 0.51-1.07), and median progression-free survival (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. Overall, OS was higher in the T+L group (11.05 months), followed by the tissue-only group (9.93 months), and the liquid-only group (4.05 months). PFS followed a similar pattern, with the longest PFS observed in the T+L group (4.93 months) compared to 3.06 months in the tissue-only group and 2.07 months in the liquid-only group. Conclusions: Although the concordance rate between tissue and liquid biopsies was only 49%, the substantial increase in detection of actionable alterations (over 60% with the addition of liquid biopsy) and significative improvement of survival outcomes observed with combined T+L concordance strongly emphasize the importance of integrating both biopsy modalities to enhance precision oncology approaches. Citation Format: Paolo Marchetti, Simone Scagnoli, Edoardo Crimini, Simona Pisegna, Sofia Verkhovskaia, Giuseppe Curigliano, Sara Lonardi, Valentina Guarneri, Chiara Cremolini, Umberto Malapelle, Ettore D. Capoluongo, Paolo A. Ascierto, Fabio Puglisi, Giancarlo Pruneri, Giulia D'Amati, Bruna Cerbelli, Mauro Biffoni, Giuseppe Tonini, Lucia Del Mastro, Andrea Botticelli. Combined tissue and liquid biopsy improves outcomes in advanced solid tumors: an exploratory analysis of the ROME trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6372.