Adnkronos Rome, April 30 (Adnkronos Salute) – In the context of the mutational model guided by the Molecular Tumor Board (MTB), patients with advanced tumors achieve significantly better survival when they receive personalized therapy based on the detection of the same genomic alteration with both tissue and liquid biopsy, compared to personalized therapy based on a single type of biopsy.
In particular, in the group of patients with concordance of the 2 tests, disease control at 12 months tripled, going from 9,1% of those treated with conventional therapy to 27,2% of those treated with molecular-targeted therapy. These results were further confirmed by the analysis of overall survival in the group of patients treated with molecular-targeted therapy: 11,05 months with concordance of the 2 tests, 9,9 months with positive solid biopsy only, and 4,05 months in the group with positive liquid biopsy only. These are the main results of an analysis of the significance of genomic profiling in the multicenter phase II Rome Trial study, presented at the American Association for Cancer Research (Aacr) Annual Meeting 2025, underway in Chicago.
"Genomic profiling," explains Paolo Marchetti, scientific director of Idi-Irccs in Rome and president of the Foundation for Personalized Medicine (Fmp), "is used in precision oncology to help identify specific alterations in a tumor, which can be the target of a therapy. Although the tests can be performed using a blood or tissue sample, it is not yet clear which method should be preferred in clinical practice and in what specific circumstances." Tissue biopsies take a sample directly from the tumor, but require an invasive surgical procedure, and because the sample is taken from a specific area of the tumor, the test may not detect mutations present elsewhere. Liquid biopsies require only a blood sample, but may not detect mutations from tumors that do not release enough DNA into the bloodstream. These differences in sample collection methods can lead to inconsistent results.
"Studying the discordance of molecular alterations between tissue and liquid biopsies is fundamental for precision oncology, especially in the mutational model," says Marchetti, who presented the results of the study at the Aacr Congress. "Tumor characteristics in different sites can facilitate the identification of different clinical targets to be pursued, but current biopsy strategies often fail to capture this heterogeneity."
Between November 2020 and August 2023 – a note informs – 1.794 adult patients with advanced or metastatic solid tumors, in second or third line of treatment, were enrolled in the Rome Trial, an independent academic study, conducted under the patronage of the University of Rome La Sapienza, the Istituto Superiore di Sanità and Fmp. Each patient provided samples for liquid (FoundationOne Liquid CDx) and tissue (FoundationOne CDx) biopsies. Next-generation sequencing was performed on the samples and the results were analyzed by a Mtb to evaluate concordance and discordance based on the alterations considered actionable (i.e. target of specific treatments). Concordance was defined as the detection of the same significant alterations in both types of biopsy. Discordance indicates the detection in only one type of biopsy. The board identified 400 patients with alterations that could be the object of personalized therapy. In these, liquid and tissue biopsies identified the same actionable alterations in 49,2% of cases (197 patients, T+L group), while actionable alterations were identified exclusively in tissue biopsy in 34,7% of cases (139 patients) and exclusively in liquid biopsy in 16% (64 patients). In both arms, patients were randomized to receive personalized therapy or standard of care based on the choice of the clinician who presented the case.
Median overall survival (OS) was 11,05 months in the T+L group receiving personalized therapy compared with 7,7 months in the standard-of-care group, representing a 26% reduction in the risk of death for patients in the T+L group. Median progression-free survival (PFS) was 4,93 months compared with 2,8 months, representing a 45% reduction in the risk of progression in the T+L group. In contrast, the survival benefit of personalized therapy was less pronounced or absent in patients with discordant results. Overall, OS was highest in the T+L group (11,05 months), followed by the tissue biopsy-only group (9,93 months) and the liquid biopsy-only group (4,05 months). PFS followed a similar trend: longer in the T+L group (4,93 months) compared with 3,06 months in the tissue biopsy-only group and 2,07 months in the liquid biopsy-only group. Additionally, the 12-month OS rate was 47,8% in the T+L group receiving personalized 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 personalized therapy arm compared with 11,8% in the standard-of-care arm.
"The better outcomes observed in patients with concordant biopsy results - Marchetti emphasizes - highlight the potential of combined molecular profiling approaches to optimize patient selection for personalized therapies. Concordance may be related to the fact that the tumor expresses the same genomic alteration in different metastatic sites. Expanding the analyses to take into account other factors, such as disease subtype, metastatic sites and biopsy type, 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 load (35%) and microsatellite instability (1%), in addition to test failure (21%). The 2 pathways with the highest discordance rates were PI3K/Pten/Akt/mTor and Erbb2.
"We have presented important data - comments Marchetti - as demonstrated by the interest of the organizing committee of the 2025 Aacr Congress, with over 22 thousand participants, and confirmatory studies have already been scheduled. Very interesting - he underlines - are the biological evaluations that derive from these data and that represent the premises for future investigations: from tumor heterogeneity to the limitations in the detection of genomic amplifications, from the low concentration of circulating DNA in some tumors to the peculiar biological characteristics of some tumors. It is necessary to develop strategies to address the discordance, for example by adopting additional molecular profiling methods or improving the sensitivity and specificity of existing technologies". Our group will also work to validate these results in a multicenter cohort using integrated liquid and tissue biopsy profiling with new analysis platforms, integrated by the use of artificial intelligence systems".
"By addressing the issues of discordance and exploiting the strengths of both biopsy modalities," concludes the specialist, "future strategies may refine precision oncology algorithms and improve clinical outcomes for patients with advanced tumors, ultimately leading, in the relatively near future, to reduce as much as possible, or eliminate entirely, the need for the more invasive biopsy of tumor tissue."