CHICAGO – A groundbreaking clinical trial presented at the American Association for Cancer Research (AACR) Annual Meeting 2025 has demonstrated that patients with advanced solid tumors experience significantly improved survival outcomes when treatment is tailored using information from both tissue and liquid biopsies. The findings from the phase II, multicenter ROME trial could redefine the approach to precision oncology and patient care.
Led by Dr. Paolo Marchetti, scientific director at the Istituto Dermopatico dell’Immacolata (IDI-IRCCS) in Rome, Italy, the study evaluated the impact of using concordant genomic data from both tissue and blood samples to select targeted therapies. According to Marchetti, investigating the differences and agreements between biopsy types is critical to capturing the full complexity of cancer mutations.
Precision Oncology: The Promise and the Challenge
Genomic profiling plays a pivotal role in precision oncology, aiming to match patients with therapies targeting specific alterations in their tumors. However, uncertainties remain about the optimal method for collecting biopsy samples in clinical practice.
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Tissue biopsies, though considered the gold standard, require invasive surgical procedures and may miss mutations occurring in other parts of a heterogeneous tumor. On the other hand, liquid biopsies offer a non-invasive alternative by analyzing circulating tumor DNA in the blood but can sometimes fail to detect mutations, especially in tumors that shed little DNA.
“These differences in collection methods can lead to discordant results between tissue and liquid biopsies,” Dr. Marchetti explained during his presentation. “Understanding and addressing this discordance is critical for the future of precision oncology.”
The Design and Scope of the ROME Trial
Between November 2020 and August 2023, the ROME trial enrolled 1,794 adult patients with advanced or metastatic solid tumors who were on second- or third-line therapy. Each participant underwent both tissue biopsy (FoundationOne CDx) and liquid biopsy (FoundationOne Liquid CDx). Next-generation sequencing was performed on the samples, and a molecular tumor board reviewed the results to assess concordance and discordance based on actionable genomic alterations.
Concordance was defined as the detection of the same actionable alterations in both biopsy types, while discordance indicated detection in only one type. Out of the total cohort, 400 patients had targetable alterations suitable for tailored therapy.
Of these 400 patients:
- 49.2% (197 patients) had concordant actionable alterations detected in both tissue and liquid biopsies (T+L group),
- 34.7% (139 patients) had actionable alterations detected only in tissue biopsies,
- 16% (64 patients) had actionable alterations detected only in liquid biopsies.
Patients within each group were then randomly assigned to receive either tailored therapy based on their genomic profile or standard-of-care treatment as determined by their physician.
Striking Survival Benefits for Concordant Biopsy Group
The results were compelling: Patients in the T+L group who received tailored therapy showed significantly better survival outcomes compared to those receiving standard-of-care treatments.
Median overall survival (OS) in the T+L tailored therapy group was 11.05 months, compared to 7.7 months in the standard-of-care group—a 26% reduction in the risk of death. Similarly, median progression-free survival (PFS) was 4.93 months for the tailored therapy group versus 2.8 months for the standard care group, corresponding to a 45% reduction in the risk of disease progression.
Additional key outcomes included:
- A 12-month OS rate of 47.8% for the T+L tailored therapy group versus 38.8% for the standard-care group.
- A 12-month PFS rate of 27.2% compared to 9.1%, respectively.
- An objective response rate of 20% in the T+L tailored therapy group versus 11.8% in the standard-care group.
In contrast, the survival benefit was notably smaller or absent among patients whose actionable alterations were identified by only one biopsy type.
Overall survival across groups:
- T+L group: 11.05 months
- Tissue-only group: 9.93 months
- Liquid-only group: 4.05 months
Progression-free survival followed the same trend, further highlighting the advantage of concordant profiling.
Understanding Discordance: A Path Forward
The study also delved into the reasons behind discordance between biopsy types. Discordant cases were attributed to:
- Detection discrepancies in molecular alterations (43.3%),
- High tumor mutational burden (35%),
- Microsatellite instability (1%),
- Test failures (21%).
The pathways with the highest rates of discordance were the PI3K/PTEN/AKT/mTOR pathway and the ERBB2 pathway.
Dr. Marchetti emphasized that addressing discordance is a crucial step forward. He proposed several strategies, including:
- Incorporating additional molecular profiling techniques,
- Enhancing the sensitivity and specificity of existing technologies,
- Expanding analyses based on disease subtype, metastatic sites, and biopsy location.
“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.
Future Directions: Toward Integrated Biopsy Strategies
Marchetti’s team plans to validate the ROME trial’s findings in a multicenter cohort study using integrated tissue and liquid profiling at multiple timepoints. By systematically capturing tumor heterogeneity and evolution over time, they hope to refine diagnostic algorithms and further enhance clinical outcomes for patients with advanced cancers.
“By addressing the challenges of discordance and leveraging the strengths of both biopsy modalities, future strategies can refine precision oncology algorithms and enhance patient outcomes,” Marchetti concluded.
Limitations and Funding Sources
The ROME trial, while promising, had several limitations:
- The exploratory nature of the analysis and absence of predefined statistical power for subgroup comparisons limit the generalizability of the findings.
- Samples for tissue and liquid biopsies were sometimes collected at different timepoints, potentially affecting comparative results.
- The relatively small sample size for the liquid-only group may limit conclusions drawn for this subset.
The trial was funded by several pharmaceutical companies, including Roche, Bristol Myers Squibb, Incyte, Novartis, Pfizer, Takeda, Merck, and Eli Lilly and Company. Dr. Marchetti disclosed consultancy and advisory roles with multiple pharmaceutical firms and participation on the advisory board of Drug-PIN Ag.
Implications for Clinical Practice
The findings from the ROME trial represent a significant advancement in the ongoing evolution of precision oncology. They underscore the importance of comprehensive genomic profiling using both tissue and liquid biopsies to maximize therapeutic success.
As oncology moves toward more personalized treatment paradigms, the integration of both biopsy methods may soon become the standard of care. Future research building on the ROME trial’s findings will likely focus on refining molecular diagnostics, improving technologies to detect subtle mutations, and better understanding the biological basis of biopsy discordance.
For patients battling advanced cancers, this tailored, dual-biopsy approach offers renewed hope for more effective, longer-lasting treatments—and potentially, a better quality of life.
