Patients with advanced solid tumors experienced significantly improved survival outcomes when receiving a tailored therapy based on the detection of the same genomic alteration in both tissue and liquid biopsies compared with both standard-of-care treatment and tailored therapy that was based on either biopsy on its own, according to results from the phase II, multicenter ROME trial presented at the American Association for Cancer Research (AACR) Annual Meeting 2025, held April 25-30.
Genomic profiling is used as part of precision oncology to help identify specific alterations in a tumor that can be targeted with a therapeutic. While tests can be performed using a blood or tissue sample, it remains unclear which method should be preferred in clinical practice and under which specific circumstances, according to Paolo Marchetti, MD, scientific director at the Istituto Dermopatico dell’Immacolata (IDI-IRCCS) in Rome, Italy.
Tissue biopsies get a sample directly from the tumor but require an invasive surgical procedure. Since the sample is taken from a specific area of the tumor, the test may miss mutations in other parts of the tumor. Liquid biopsies only require a sample of blood but may not detect mutations from tumors that do not shed enough cells into the bloodstream. These differences in how samples are collected can lead to discordant results.
“Investigating discordance in molecular alterations between tissue and liquid biopsies is critical for precision oncology,” explained Marchetti, who presented the trial results. “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.”
Between November 2020 and August 2023, 1,794 adult patients with advanced or metastatic solid tumors who were on their second or third line of treatment were enrolled in the ROME trial. Each patient was required to provide samples for both liquid (FoundationOne Liquid CDx) and tissue (FoundationOne CDx) biopsies. Next-generation sequencing was performed on the samples and the results were analyzed by a molecular tumor board to assess both concordance and discordance based on alterations considered actionable. Concordance was defined as the detection of the same significant alterations in both biopsy types; discordance indicated detection in only one. The board identified 400 patients with alterations that could be targeted with tailored therapy.
Of these 400 patients, tissue and liquid biopsies identified the same actionable alterations in 49.2% of cases (197 patients, T+L group), while actionable alterations were exclusively detected via tissue biopsy in 34.7% of cases (139 patients) and exclusively in liquid biopsies in 16% (64 patients). In each arm, patients were randomly assigned to receive either tailored therapy or standard of care as chosen by the clinician presenting the case.
Median overall survival (OS) was 11.05 months in the T+L group that received tailored therapy vs. 7.7 months in the standard-of-care group, with a 26% reduction in the risk of death for those in the T+L group. The median progression-free survival (PFS) in these groups was 4.93 months vs. 2.8 months, respectively, with a 45% reduction in the risk of progression in the T+L group. In contrast, the survival benefit of tailored therapy was less pronounced or absent in patients with discordant results. Overall, OS was higher 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). PFS followed a similar pattern, with the longest PFS in the T+L group (4.93 months) vs. 3.06 months in the tissue-only group and 2.07 months in the liquid-only group.
Additionally, the 12-month OS rate was 47.8% in the T+L group that received tailored 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 tailored therapy arm vs. 11.8% in standard-of-care arm.
“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. “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.”
Discordant cases were attributed to discrepancies found in the detection of molecular alterations (43.3%), high tumor mutational burden (35%), and microsatellite instability (1%), as well as test failures (21%). The two pathways with the highest discordance rates were PI3K/PTEN/AKT/mTOR and ERBB2.
Marchetti said that strategies need to be developed to address discordance, such as by incorporating additional molecular profiling methods or enhancing the sensitivity and specificity of existing technologies. His group will also work to validate these findings in a multicenter cohort using integrated liquid and tissue profiling at serial timepoints.
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.”
Paolo Marchetti, MD, scientific director, Istituto Dermopatico dell’Immacolata (IDI-IRCCS), Rome
Limitations of this study include the exploratory nature of the analysis and the absence of predefined statistical power for subgroup comparisons, which limit the generalizability of the findings. Samples for the tissue and liquid biopsies were taken at different times, which may have affected the results. Finally, the relatively small size of certain subgroups, particularly the liquid-only group, may limit the robustness of conclusions for these populations.
The trial was funded by Roche, Bristol Myers Squibb, Incyte, Novartis, Pfizer, Takeda, Merck, and Eli Lilly and Company. Marchetti has had a consultant/advisory role for Bristol Myers Squibb, Roche/Genentech, MSD, Novartis, Amgen, Merck Serono, Pierre Fabre, and Incyte. He is also a member of the advisory board of Drug-PIN Ag.
date: 2025-04-30 01:33:00
Tailored Treatment Guided by Dual Biopsy approach May Improve Outcomes for Patients with Advanced Cancers
Table of Contents
- Tailored Treatment Guided by Dual Biopsy approach May Improve Outcomes for Patients with Advanced Cancers
- Understanding the Limitations of Standard Biopsies in Advanced Cancer Care
- The dual Biopsy Approach: A More Comprehensive View
- The Role of Genomic Analysis in tailoring Cancer Treatment
- Clinical Applications and Success Stories
- Practical Tips and Considerations for Patients and Physicians
- first-Hand Experience: Patient Perspectives
- Addressing the Challenges and Future Directions
- emerging Technologies further Refine the Process
Advanced cancers present a notable challenge in oncology. Traditional treatment strategies often employ a one-size-fits-all approach, which can lead to suboptimal outcomes adn unnecessary side effects. However, emerging research suggests that a dual biopsy approach, combined with advanced genomic analysis, can pave the way for more tailored cancer treatments, ultimately leading to improved survival rates and quality of life for patients battling advanced stage disease.
Understanding the Limitations of Standard Biopsies in Advanced Cancer Care
The standard biopsy, traditionally used for cancer diagnosis and staging, typically involves extracting a single tissue sample from the primary tumor site. While this provides valuable details about the cancer’s initial characteristics, it frequently enough fails to capture the full complexity and heterogeneity of advanced cancers. In advanced stages, cancer cells can spread (metastasize) to different parts of the body, and these metastatic sites may exhibit different genetic mutations and drug sensitivities compared to the primary tumor. Relying solely on a single biopsy can therefore lead to an incomplete and possibly misleading understanding of the disease.
Here’s why a single biopsy may fall short:
- Tumor Heterogeneity: Cancers are not homogenous entities; thay consist of diverse subpopulations of cells,each with varying genetic profiles and treatment responses. A single biopsy only represents a snapshot of this complex landscape.
- Evolution of Cancer Cells: Over time, cancer cells evolve and acquire new mutations, especially under selective pressure from treatment.A primary tumor biopsy taken at initial diagnosis may not reflect the current genetic makeup of the disease after treatment or during progression.
- Metastatic Spread: Metastatic sites can harbor distinct genetic alterations compared to the primary tumor, influencing treatment response. Ignoring these differences can lead to treatment failure.
The dual Biopsy Approach: A More Comprehensive View
The dual biopsy approach addresses the limitations of standard biopsies by obtaining tissue samples from both the primary tumor and at least one metastatic site. This allows for a more comprehensive assessment of the cancer’s genetic landscape, including the identification of both shared and unique mutations across different sites. The information gained from analyzing these biopsies can then be used to personalize treatment strategies, selecting therapies that are most likely to be effective against the specific characteristics of each patient’s cancer. In certain specific cases,liquid biopsies are used as alternatives when tissue biopsies are not feasible.Liquid biopsies analyse circulating tumor DNA (ctDNA) in the blood.
Key Benefits of the Dual Biopsy Approach:
- Improved Treatment Selection: By identifying specific genetic mutations,physicians can select targeted therapies that are most likely to be effective,while avoiding treatments that are unlikely to provide benefit.
- Personalized Medicine: Tailoring treatment based on the unique genetic profile of each patient’s cancer maximizes the chances of a positive response.
- Minimized Side Effects: By targeting specific mutations, treatments can be more precise, reducing the risk of off-target effects and side effects.
- monitoring Treatment Response: Serial biopsies (or liquid biopsies) can be used to monitor how the cancer is responding to treatment and to detect the emergence of new mutations that may confer resistance.
The Role of Genomic Analysis in tailoring Cancer Treatment
The success of the dual biopsy approach hinges on the use of advanced genomic analysis techniques, such as next-generation sequencing (NGS).NGS allows for the rapid and comprehensive sequencing of large numbers of genes, providing a detailed picture of the cancer’s genetic makeup. The identified mutations can then be matched with specific targeted therapies or clinical trials that are designed to target those mutations. This ability to link genomic information with therapeutic options is transforming the landscape of cancer care.
How Genomic Analysis Works:
- DNA Extraction: DNA is extracted from the biopsy samples.
- Library Preparation: The DNA is prepared for sequencing.
- Sequencing: NGS technology is used to sequence the DNA, identifying the order of the building blocks.
- data Analysis: bioinformatics tools are used to analyze the sequencing data and identify genetic mutations.
- Interpretation: Oncologists and molecular biologists interpret the results, matching mutations with potential therapeutic targets.
Clinical Applications and Success Stories
The dual biopsy approach is being increasingly implemented in clinical practise for a variety of advanced cancers, including lung cancer, breast cancer, colon cancer, and melanoma. Several studies have demonstrated the potential of this approach to improve patient outcomes. Such as, in patients with advanced non-small cell lung cancer (NSCLC), dual biopsies have been used to identify mutations in genes such as EGFR, ALK, and ROS1, which are targetable with specific tyrosine kinase inhibitors (TKIs). Identifying these mutations through dual biopsy and subsequent treatment with a TKI has shown significant improvements in progression-free survival and overall survival.
Table: Examples of Targetable Mutations Identified via Dual Biopsy
| Cancer Type | Targetable Mutation | Targeted Therapy |
|---|---|---|
| NSCLC | EGFR | Erlotinib, Gefitinib, Osimertinib |
| Melanoma | BRAF V600E | Vemurafenib, Dabrafenib |
| Breast Cancer | HER2 amplification | Trastuzumab, Pertuzumab |
| Colon Cancer | KRAS G12C | Sotorasib |
Moreover, some institutions are using dual biopsies to identify mechanisms of resistance to previous therapies. By sampling both the primary tumor and a metastatic site after treatment failure, physicians can pinpoint the mutations that have driven resistance, allowing for the selection of second-line or third-line therapies that can overcome this resistance.
Practical Tips and Considerations for Patients and Physicians
Implementing a dual biopsy approach requires careful planning and coordination between oncologists, radiologists, pathologists, and molecular biologists. Several practical considerations are important to ensure the success of this strategy:
- Patient Selection: Identifying patients who are most likely to benefit from a dual biopsy approach is crucial. This includes patients with advanced cancers who have failed standard therapies or who have evidence of significant tumor heterogeneity.
- Biopsy Technique: Choosing the appropriate biopsy technique (e.g., core needle biopsy, surgical biopsy) is essential to obtain sufficient tissue for genomic analysis. image-guided biopsies can help ensure that the samples are taken from representative areas of the tumor.
- Sample Processing: Proper handling and processing of the biopsy samples are critical to preserve the integrity of the DNA and RNA. This includes prompt fixation and storage of the samples according to established protocols.
- Turnaround Time: Rapid turnaround time for genomic analysis is important to allow for timely treatment decisions. Laboratories should strive to provide results within a clinically relevant timeframe.
- multidisciplinary Collaboration: Effective interaction and collaboration between different specialists are essential to interpret the genomic data and make appropriate treatment recommendations.
Ensuring Accurate Results
To make sure laboratory testing delivers reliable insights, it’s vital that:
- The lab has the needed expertise: Look for laboratories with a proven track record in cancer genomic testing.
- Accuracy is paramount: Choose labs prioritizing accuracy in both sample handling and data analysis.
- Testing is comprehensive: Ensure testing covers all relevant sets of genes and actionable biomarkers.
- Expert review is involved: Look for a pathologist-led review that makes sure data from tests are accurately interpreted.
first-Hand Experience: Patient Perspectives
While the dual biopsy approach holds great promise, it’s crucial to consider the patient experience. Undergoing multiple biopsies can be physically and emotionally challenging. Patients may experience pain, anxiety, and uncertainty about the results.Open communication between the medical team and the patient is essential to address these concerns and provide support throughout the process. Understanding the potential benefits and limitations of the approach can definitely help patients make informed decisions about their treatment.
One patient, Sarah, diagnosed with metastatic breast cancer, shared her experience: “Initially, I was apprehensive about having two biopsies, but my doctor explained how it could help personalize my treatment. Learning that my metastatic site had a different mutation than my primary tumor was eye-opening.It led to a targeted therapy that has significantly improved my quality of life.” Another point of view: ‘I had a liquid biopsy and a tissue biopsy. The liquid biopsy was less painful and felt less invasive than a standard biopsy procedure.’
Addressing the Challenges and Future Directions
While the dual biopsy approach offers significant advantages, it also faces challenges. These include the cost of genomic analysis, the limited availability of targeted therapies for certain mutations, and the potential for false-negative or false-positive results. Overcoming these challenges will require ongoing research and development, as well as increased access to affordable genomic testing. Future directions in this field include:
- development of new targeted therapies: Investing in research to develop new drugs that target specific cancer mutations is crucial to expand the treatment options available to patients.
- Integration of artificial intelligence (AI): AI can be used to analyze complex genomic data and identify novel therapeutic targets.
- Liquid biopsies: Liquid biopsies, which analyze circulating tumor DNA in the blood, offer a less invasive alternative to tissue biopsies and can be used to monitor treatment response and detect the emergence of resistance mutations.
- Clinical trials: More clinical trials are needed to evaluate the effectiveness of dual biopsy-guided therapy in different cancer types and to identify the optimal strategies for patient selection and treatment personalization.
emerging Technologies further Refine the Process
Beyond dual biopsy, continual advancements in cancer diagnostics are further fine-tuning personalized medicine. These techniques aim to give doctors a more detailed and dynamic understanding of cancer cells’ behavior. One technology is called “single-cell sequencing”, which examines the genetic map of individual cancer cells. This helps doctors identify rare, drug-resistant cells, which may not be detectable with the whole-tumor examination.Another technique is “real-time monitoring of cancer cells”. It measures drug responses of cancer cells through artificial intelligence technology. This helps doctors choose a particular medicine more quickly for the cancer patient.
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