Patients battling advanced solid tumors have shown notably improved survival rates when their treatment was guided by genomic alterations identified in both tissue and liquid biopsies, reveals compelling new data from the phase II ROME trial. Presented at the prestigious American Association for Cancer Research (AACR) Annual Meeting 2025, these findings illuminate the critical role of concordant molecular profiling in precision oncology, emphasizing the transformative potential of integrating multiple biopsy methods to tailor cancer therapy more effectively.
Precision oncology hinges on detecting key genetic mutations that drive tumor growth and response to therapy. Traditionally, tumor tissue biopsies have served as the gold standard for such profiling by directly sampling the tumor. However, tissue biopsies require invasive procedures, and because samples are taken from localized tumor regions, they risk missing the broader spectrum of genetic heterogeneity intrinsic to many cancers. Conversely, liquid biopsies analyze circulating tumor DNA fragments shed into the bloodstream, offering a less invasive alternative that theoretically captures tumor diversity more comprehensively. Yet, their sensitivity is limited by how much tumor DNA enters circulation, potentially leading to incomplete or false-negative genomic profiles.
The ROME trial was designed to rigorously compare outcomes based on genomic profiling concordance between paired tissue and liquid biopsies. Enrolling nearly 1,800 patients with advanced or metastatic solid tumors from multiple centers between late 2020 and mid-2023, the trial mandated that all participants submit samples for both FoundationOne CDx tissue and FoundationOne Liquid CDx assays. These next-generation sequencing (NGS) platforms interrogate hundreds of cancer-associated genes to detect alterations deemed actionable—those with potential targeted therapies—via a molecular tumor board’s expert analysis.
Out of these patients, the tumor board identified 400 individuals harboring actionable genomic alterations. Strikingly, just under half (49.2%) exhibited concordant actionable mutations detected in both tissue and liquid biopsies (the T+L group). Another 34.7% had alterations found exclusively in tissue samples, while 16% had them exclusively in liquid biopsies. This discordance underscores the complexity of tumor biology and the technical limitations of each biopsy method when deployed in isolation.
The survival benefits of guiding therapy using concordant biopsy findings were profound. Patients in the T+L group receiving matched targeted therapy experienced a median overall survival (OS) of 11.05 months, significantly surpassing the 7.7 months observed in patients receiving standard-of-care treatments. This corresponded to a substantial 26% risk reduction in death. Median progression-free survival (PFS) in this group also nearly doubled to 4.93 months versus 2.8 months in controls, reflecting a 45% decrease in disease progression risk. These figures highlight the potency of combining molecular insights across biopsy platforms to more precisely identify therapeutic targets.
In contrast, patients whose actionable alterations were identified through only one biopsy type showed attenuated benefits from tailored therapy. The median OS for those with tissue-only actionable findings was 9.93 months, while those with liquid-only findings fared worst at 4.05 months. Progression-free survival followed a corresponding gradient, further underscoring that concordance between both biopsy methods correlates with superior clinical outcomes, likely due to a more accurate and comprehensive understanding of tumor genomics.
Importantly, the trial also revealed higher objective response rates in the T+L tailored therapy group at 20%, compared with 11.8% among patients receiving standard care. The 12-month OS and PFS rates further reinforced these trends, with nearly half of patients in the concordant group alive after one year and over a quarter free from progression, compared to markedly lower rates in standard-care cohorts. These statistics underpin the clinical relevance and potential practice-changing impact of leveraging concordant molecular profiles.
The molecular tumor board attributed discordance primarily to detection variances—where mutations were seen in one assay but not the other—in 43.3% of cases. Additional causes included high tumor mutational burden (35%), microsatellite instability (1%), and technical issues such as test failures in 21%. Notably, pathways such as PI3K/PTEN/AKT/mTOR and ERBB2 signaling displayed the greatest rates of discordance, suggesting that certain genomic contexts remain challenging to detect consistently across biopsy types.
Dr. Paolo Marchetti, who led the ROME trial analysis, highlighted the implications of these findings for the evolution of precision oncology diagnostics. He pointed out that the presence of the same actionable tumor genomic alterations at different metastatic sites may explain the survival advantage seen with concordant profiling. By expanding analyses to integrate additional clinical variables such as disease subtype, biopsy timing, and metastatic location, future diagnostic algorithms can become more refined and predictive.
The study authors acknowledged important limitations: as an exploratory trial, it lacked predefined power for subgroup analyses, which limits the strength and generalizability of some conclusions. Additionally, tissue and liquid biopsy samples were collected at different time points, reflecting real-world complexities but potentially influencing concordance rates. The relatively smaller size of certain subgroups, particularly the liquid-only cohort, also calls for cautious interpretation.
Looking ahead, the research team advocates for strategies to overcome discordance—including combining additional molecular profiling modalities and enhancing assay sensitivity—to better capture tumor heterogeneity. Plans are underway to validate these findings in larger multicenter cohorts using integrated liquid and tissue profiling at multiple timepoints throughout therapy, aiming to develop more dynamic and adaptable diagnostic protocols.
Marchetti emphasized that addressing the technical and biological challenges of discordance will be essential to fully maximize the benefits of precision oncology, enabling truly personalized treatment strategies that improve clinical outcomes for patients with advanced cancers. The ROME trial thus sets a critical precedent for the future integration of liquid and tissue biopsies in routine clinical decision-making.
The ROME trial was supported by major pharmaceutical stakeholders including Roche, Bristol Myers Squibb, Incyte, Novartis, Pfizer, Takeda, Merck, and Eli Lilly and Company. Dr. Marchetti disclosed consultant and advisory roles with multiple industry partners active in oncology drug development. His commitment exemplifies the collaborative interface between clinical research and pharmaceutical innovation needed to drive forward tailored cancer care.
These groundbreaking results not only reaffirm the importance of genomic profiling in oncology but also underscore the nuanced complexity of tumor heterogeneity and the urgent need to optimize biopsy strategies. As the field moves toward increasingly personalized and adaptive cancer therapies, integrating concordant multi-modal molecular diagnostics promises to reshape standard-of-care paradigms and enhance survival prospects for patients confronting advanced solid tumors.
Subject of Research: Precision oncology through concordant genomic profiling in tissue and liquid biopsies for advanced solid tumors
Article Title: Concordant Genomic Alterations in Tissue and Liquid Biopsies Enhance Survival in Advanced Solid Tumors, ROME Trial Shows
News Publication Date: April 2025
Web References:
- ROME Trial ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT04591431
- AACR Annual Meeting 2025: https://www.aacr.org/meeting/aacr-annual-meeting-2025/
Keywords:
- Tumor tissue
- Biopsies
- Cancer treatments
- Precision oncology
- Liquid biopsy
- Tissue biopsy
- Next-generation sequencing
- Genomic alterations
- Advanced solid tumors
- Molecular profiling
- Targeted therapy
- Tumor heterogeneity
