AACR 2025: Tailored Treatment Guided by Combined Tissue and Liquid Biopsies May Improve Outcomes in Advanced Solid Tumors

Emerging data from the phase 2, multicenter ROME trial (NCT04591431) presented at the American Association for Cancer Research (AACR) Annual Meeting 2025 in Chicago, Illinois, provide evidence that combining tissue and liquid biopsies to guide tailored therapy can lead to significantly improved patient outcomes compared with using either biopsy alone or standard of care (SOC). According to AACR presenter and ROME trial investigator Paolo Marchetti, MD, scientific director at the Istituto Dermopatico dell’Immacolata (IDI-IRCCS) in Rome, Italy, the trial results highlight emerging opportunities in the application of precision oncology to clinical practice.

“Investigating discordance in molecular alterations between tissue and liquid biopsies is critical for precision oncology,” Marchetti said in an AACR statement. “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.”

Human cell tissue under microscope in pathology laboratory. Image Credit: © DMH - stock.adobe.com

Tissue biopsies have long been considered the gold standard for tumor genomic profiling. They offer the advantage of direct sampling from the tumor mass but are invasive and may miss heterogeneity due to sampling limitations. Liquid biopsies, utilizing circulating tumor DNA (ctDNA) from blood samples, are minimally invasive and can capture broader tumor heterogeneity, but their sensitivity can be limited in tumors that shed little DNA. These fundamental differences have sparked debate regarding how best to incorporate each method into clinical workflows.

In the ROME trial, which enrolled 1794 patients with advanced or metastatic solid tumors between November 2020 and August 2023, patients underwent genomic profiling using both FoundationOne CDx (tissue) and FoundationOne Liquid CDx (blood). A centralized molecular tumor board reviewed the sequencing results, identifying 400 patients with actionable alterations eligible for tailored therapy. Among these, actionable alterations were concordantly detected in both biopsy types in 49.2% of patients (T+L group), while 34.7% had actionable alterations detected only via tissue biopsy and 16% only through liquid biopsy. These findings underscore the fact that no single biopsy method can fully capture the molecular complexity of advanced tumors.

Patients in each group were randomized to receive either a tailored therapy based on their genomic profile or SOC treatment selected by their treating oncologist. The results showed that patients in the T+L group who received tailored therapy experienced a median overall survival (OS) of 11.05 months, compared to 7.7 months in those receiving SOC. This translates to a 26% reduction in the risk of death (hazard ratio [HR] 0.74; 95% CI: 0.51-1.07). Similarly, median progression-free survival (PFS) was significantly longer at 4.93 months vs 2.8 months, corresponding to a 45% reduction in the risk of disease progression (HR 0.55; 95% CI: 0.40-0.76).

Importantly, the survival benefit associated with tailored therapy was most pronounced in patients with concordant biopsy findings. Among discordant cases—where actionable alterations were detected only in one type of biopsy—tailored therapy yielded less impressive benefits, highlighting the critical value of concordance between tissue and liquid profiling. Overall, OS was highest 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). The PFS data mirrored this trend, further emphasizing the clinical advantage of dual-biopsy concordance.

“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 in an AACR statement. “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.”

The study also provided insight into the reasons for discordance. Among the discordant cases, discrepancies in the detection of molecular alterations accounted for 43.3%, while high tumor mutational burden differences contributed 35%, microsatellite instability differences 1%, and technical test failures 21%. Notably, discordance was highest in alterations within the PI3K/PTEN/AKT/mTOR and ERBB2 pathways, suggesting that additional refinement of testing methodologies may be particularly critical in these molecular contexts.

The objective response rate among patients in the T+L cohort who received tailored therapy was 20%, compared to 11.8% in those receiving SOC. Furthermore, the 12-month OS rate was notably higher in the T+L tailored therapy group (47.8%) vs the SOC group (38.8%). The 12-month PFS rates further underscored the benefit, at 27.2% in the tailored therapy arm compared to 9.1% with SOC.

However, Marchetti and his study co-authors noted that the trial had several limitations, such as the exploratory nature of the analysis, the lack of predefined statistical power for subgroup comparisons, and the timing difference between tissue and liquid sample collection; these could all influence the results. Additionally, the small size of some subgroups, especially the liquid-only cohort, limits the robustness of the results in these populations.

Nonetheless, the implications for clinical practice are notable. The ROME trial results suggest that integrating both tissue and liquid biopsy results could optimize patient selection for targeted therapies, improving clinical outcomes in a way that is not possible through single-modality profiling.

Marchetti also emphasized the need for further strategies to address discordance.

“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 in an AACR statement.

Looking forward, the ROME investigators plan to validate these findings in a multicenter cohort using serial sampling. Such work could pave the way toward a more dynamic, real-time approach to precision oncology, adapting treatments as the tumor evolves under therapeutic pressure.

For oncology pharmacists, these results reinforce the growing importance of molecular diagnostics in optimizing cancer care. Pharmacists will increasingly play a vital role not only in selecting and managing targeted therapies but also in interpreting complex genomic data in collaboration with oncologists and molecular tumor boards. As precision oncology evolves, so too must the pharmacist’s skill set, ensuring patients receive therapies tailored not just to their cancer type, but to the very genomic underpinnings of their disease.

In summary, the ROME trial provides evidence to support a combined tissue-plus-liquid biopsy strategy to guide therapy decisions in advanced solid tumors. While challenges such as discordance remain, the survival benefits observed underscore that a dual-biopsy approach may become a new standard in precision oncology.

REFERENCE

Patient Outcomes May Improve With Tailored Treatment Guided by Tissue Plus Liquid Biopsies vs Individually. AACR Annual Meeting. April 29, 2025. Accessed April 28, 2025. https://aacr.ent.box.com/s/uojb36q195jvga6ubmokbni8zqpmks2z