CHICAGO – Patients with advanced solid tumors experienced significantly improved survival outcomes when receiving a tailored therapy based on the detection of the same genomic alteration in both tissue and liquid biopsies compared with both standard-of-care treatment and tailored therapy that was based on either biopsy on its own, according to results from the phase II, multicenter ROME trial presented at the American Association for Cancer Research (AACR) Annual Meeting 2025 , held April 25-30.
Genomic profiling is used as part of precision oncology to help identify specific alterations in a tumor that can be targeted with a therapeutic. While tests can be performed using a blood or tissue sample, it remains unclear which method should be preferred in clinical practice and under which specific circumstances, according to Paolo Marchetti, MD , scientific director at the Istituto Dermopatico dell'Immacolata (IDI-IRCCS) in Rome, Italy.
Tissue biopsies get a sample directly from the tumor but require an invasive surgical procedure. Since the sample is taken from a specific area of the tumor, the test may miss mutations in other parts of the tumor. Liquid biopsies only require a sample of blood but may not detect mutations from tumors that do not shed enough cells into the bloodstream. These differences in how samples are collected can lead to discordant results.
"Investigating discordance in molecular alterations between tissue and liquid biopsies is critical for precision oncology," explained Marchetti, who presented the trial results. "Tumor characteristics in different sites can lead to the identification of different clinical actionable targets, yet current biopsy strategies often fail to capture this heterogeneity."
Between November 2020 and August 2023, 1,794 adult patients with advanced or metastatic solid tumors who were on their second or third line of treatment were enrolled in the ROME trial. Each patient was required to provide samples for both liquid (FoundationOne Liquid CDx) and tissue (FoundationOne CDx) biopsies. Next-generation sequencing was performed on the samples and the results were analyzed by a molecular tumor board to assess both concordance and discordance based on alterations considered actionable. Concordance was defined as the detection of the same significant alterations in both biopsy types; discordance indicated detection in only one. The board identified 400 patients with alterations that could be targeted with tailored therapy.
Of these 400 patients, tissue and liquid biopsies identified the same actionable alterations in 49.2% of cases (197 patients, T+L group), while actionable alterations were exclusively detected via tissue biopsy in 34.7% of cases (139 patients) and exclusively in liquid biopsies in 16% (64 patients). In each arm, patients were randomly assigned to receive either tailored therapy or standard of care as chosen by the clinician presenting the case.
Median overall survival (OS) was 11.05 months in the T+L group that received tailored therapy vs. 7.7 months in the standard-of-care group, with a 26% reduction in the risk of death for those in the T+L group. The median progression-free survival (PFS) in these groups was 4.93 months vs. 2.8 months, respectively, with a 45% reduction in the risk of progression in the T+L group. In contrast, the survival benefit of tailored therapy 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 in the T+L group (4.93 months) vs. 3.06 months in the tissue-only group and 2.07 months in the liquid-only group.
Additionally, the 12-month OS rate was 47.8% in the T+L group that received tailored therapy and 38.8% in the standard-of-care group, while the 12-month PFS rates were 27.2% and 9.1%, respectively. Among T+L patients, the objective response rate was 20% in the tailored therapy arm vs. 11.8% in standard-of-care arm.
"The superior outcomes observed in patients with concordant biopsy findings highlight the potential of combined molecular profiling approaches to optimize patient selection for tailored therapies," Marchetti said. "The concordance may be related to the tumor expressing the same genomic alteration in different metastatic sites. Expanding the analyses to account for more factors, such as disease subtype, metastatic sites, and biopsy location could help define a new, more effective diagnostic pathway."
Discordant cases were attributed to discrepancies found in the detection of molecular alterations (43.3%), high tumor mutational burden (35%), and microsatellite instability (1%), as well as test failures (21%). The two pathways with the highest discordance rates were PI3K/PTEN/AKT/mTOR and ERBB2.
Marchetti said that strategies need to be developed to address discordance, such as by incorporating additional molecular profiling methods or enhancing the sensitivity and specificity of existing technologies. His group will also work to validate these findings in a multicenter cohort using integrated liquid and tissue profiling at serial timepoints.
"By addressing the challenges of discordance and leveraging the strengths of both biopsy modalities, future strategies can refine precision oncology algorithms and enhance clinical outcomes for patients with advanced cancers," Marchetti said.
Limitations of this study include the exploratory nature of the analysis and the absence of predefined statistical power for subgroup comparisons, which limit the generalizability of the findings. Samples for the tissue and liquid biopsies were taken at different times, which may have affected the results. Finally, the relatively small size of certain subgroups, particularly the liquid-only group, may limit the robustness of conclusions for these populations.
The trial was funded by Roche, Bristol Myers Squibb, Incyte, Novartis, Pfizer, Takeda, Merck, and Eli Lilly and Company. Marchetti has had a consultant/advisory role for Bristol Myers Squibb, Roche/Genentech, MSD, Novartis, Amgen, Merck Serono, Pierre Fabre, and Incyte. He is also a member of the advisory board of Drug-PIN Ag.
