Although next-generation sequencing to assist decision-making for genomics-driven therapy in patients with advanced solid tumors has traditionally been conducted using tissue biopsy samples, recent data support the use of plasma-based circulating tumor DNA (ctDNA) for the genomic profiling of solid cancers. However, which method is more accurate and under which clinical circumstances should tissue or liquid biopsy be used are still under investigation.
The results of the phase II ROME trial suggest that patient outcomes may improve when tailored treatment is guided by integrating both tissue and liquid biopsies compared with either one individually. Findings from the study showed that patients with advanced solid tumors experienced significantly improved survival outcomes after receiving a tailored therapy based on the detection of the same genomic alteration in both tissue and liquid biopsies compared with standard-of-care treatment and tailored therapy that was based on either biopsy alone. The study, conducted by Paolo Marchetti, MD, Scientific Director at the Istituto Dermopatico dell’Immacolata (IDI-IRCCS), Rome, and colleagues, was presented during the 2025 American Association for Cancer Research (AACR) Annual Meeting (Abstract 6372).
Study Methodology
The researchers enrolled 1,794 patients with advanced solid tumors between November 2020 and August 2023. At the time of enrollment, the patients had received their second- or third-line treatment. Centralized next-generation sequencing was performed on both tissue and liquid biopsies using FoundationOne CDx and FoundationOne Liquid CDx tests. A centralized molecular tumor board reviewed the results to identify actionable alterations and identified 400 patients with alterations that could be targeted with tailored therapy.
This exploratory analysis evaluated the concordance between tissue and liquid biopsy results in detecting actionable alterations in the intention-to-treat population. Concordance was defined as the detection of the same significant alterations in both biopsy types; discordance indicated detection in one type alone. Overall survival and progression-free survival outcomes were analyzed across concordance groups. Because of the exploratory nature of the analysis, statistical significance was not determined.
Key Results
The researchers found that concordance between tissue and liquid 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% were attributed to discordant high-tumor mutational burden detection, 1% were attributed to microsatellite instability discrepancies, and 43.3% were attributed 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 tissue and liquid biopsies group receiving tailored therapy experienced significantly improved survival outcomes. Median overall survival was 11.1 vs 7.7 months in the standard-of-care group (hazard ratio [HR] = 0.74; 95% confidence interval [CI] = 0.51–1.07). Median progression-free survival was 4.9 vs 2.8 months (HR = 0.55; 95% CI = 0.40–0.76).
KEY POINTS
- In the phase II ROME trial, patients with advanced solid tumors experienced significantly improved survival outcomes after receiving a tailored therapy based on the detection of the same genomic alteration in both tissue and liquid biopsies compared with standard-of-care treatment and tailored therapy that was based on either biopsy alone.
- These findings support integrating both tissue and liquid modalities to enhance precision oncology approaches.
In contrast, the survival benefit of tailored therapy was less pronounced or absent in patients with discordant results. Overall, overall survival was higher in the tissue and liquid biopsies group (11.1 months), followed by the tissue biopsy–alone group (9.9 months), and the liquid biopsy–alone group (4.1 months). Progression-free survival followed a similar pattern, with the longest progression-free survival observed in the tissue and liquid biopsies group (4.9 months) compared with 3.1 months in the tissue biopsy–alone group and 2.1 months in the liquid biopsy–alone group.
“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 [tissue + liquid biopsies] concordance strongly emphasize the importance of integrating both biopsy modalities to enhance precision oncology approaches,” concluded the study authors.
Clinical Significance
“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,” said Dr. Marchetti. “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.… 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.”
Disclosure: Funding for this study was provided by Roche, Bristol Myers Squibb, Incyte, Novartis, Pfizer, Takeda, Merck, and Eli Lilly and Company. For full disclosures of the study authors, visit abstractsonline.com.
