ROME Trial Demonstrates Precision Oncology Benefits in Advanced Solid Tumors
Key Insights
The randomized phase 2 ROME trial showed that genomically matched tailored therapy significantly improved overall response rates (17.5% vs 10.0%) and progression-free survival compared to standard care in 400 patients with advanced solid tumors (search).
Patients receiving tailored treatment had a median progression-free survival of 3.5 months versus 2.8 months with standard care, with 22% remaining progression-free at 12 months compared to only 8.3% in the control group.
The molecular tumor board approach proved essential for treatment selection, with particularly strong benefits observed in patients with MSI-H tumors (search) (57% response rate), BRAF mutations, and HER2 alterations (search).
The randomized phase 2 ROME trial has provided the first robust evidence that genomically matched therapies guided by molecular tumor boards can significantly improve outcomes in patients with advanced solid tumors (search). Conducted across 40 Italian cancer centers, the study demonstrated meaningful clinical benefits for precision oncology approaches in heavily pretreated patients.
Study Design and Patient Population
Between October 2020 and July 2023, researchers screened 1,794 patients with metastatic solid tumors (search) across Italy. Of these, 897 patients with potentially actionable molecular alterations were evaluated by a multidisciplinary molecular tumor board (MTB), ultimately leading to 400 patients being randomized 1:1 to receive either tailored treatment (TT) or standard of care (SoC).
The MTB consisted of oncologists, pathologists, geneticists, bioinformaticians, and other specialists who made treatment recommendations based on comprehensive genomic profiling using FoundationOne CDx testing. Patients had an ECOG performance status of 0-1 and had received one or two prior lines of therapy.
Primary Efficacy Results
The trial met its primary endpoint, demonstrating a statistically significant improvement in overall response rate (ORR) for tailored therapy. The TT arm achieved an ORR of 17.5% (95% CI: 12.5-23.5), including 3% complete responses and 14.5% partial responses, compared to 10.0% (95% CI: 6.2-15.0) in the SoC arm, with all responses being partial (P = 0.0294).
Progression-free survival showed even more pronounced benefits. Median PFS was 3.5 months for TT versus 2.8 months for SoC (HR = 0.66, 95% CI: 0.53-0.82; P = 0.0002). The durability of response was particularly striking, with 22.0% of TT patients remaining progression-free at 12 months compared to only 8.3% in the SoC arm.
Survival and Secondary Endpoints
Overall survival did not reach statistical significance, with median OS of 9.1 months for TT versus 7.9 months for SoC (HR = 0.92, 95% CI: 0.72-1.19; P = 0.53). The high crossover rate of approximately 59% from SoC to TT after disease progression likely contributed to this lack of OS benefit.
Secondary endpoints favored the tailored treatment approach. Time to treatment failure was 3.5 months for TT versus 2.8 months for SoC (HR = 0.64, P < 0.0001), while time to next treatment was 5.0 months versus 3.5 months respectively (HR = 0.59, P < 0.0001).
Biomarker Subgroup Analysis
Exploratory analyses revealed particularly strong benefits in specific molecular subgroups. Among 18 patients with microsatellite instability-high (MSI-H (search)) tumors, the ORR was 57.1% in the TT arm versus 0% in the SoC arm. Progression-free survival had not been reached in the TT arm at the time of analysis, compared to 2.8 months in the SoC arm (HR = 0.15, 95% CI: 0.03-0.73).
Patients with high tumor mutational burden (hTMB, ≥10 mutations per megabase) showed an ORR of 25.7% with TT versus 15.4% with SoC. The 12-month PFS rate was 32.6% for TT compared to 8.1% for SoC, representing a 25% absolute improvement.
BRAF-altered tumors (search) demonstrated remarkable benefits, with PFS not reached in the TT arm versus 2.0 months in the SoC arm (HR = 0.07, 95% CI: 0.01-0.67). Similarly, patients with HER2 alterations (search) had a median PFS of 4.6 months with TT versus 2.6 months with SoC (HR = 0.40, 95% CI: 0.24-0.74).
Safety Profile
The safety profile favored tailored treatment, with grade ≥3 adverse events occurring in 40% of TT patients versus 52.5% of SoC patients. The most common adverse event in the TT arm was diarrhea (5.5%), while neutropenia was most frequent in the SoC arm (8%).
Clinical Implications
The ROME trial establishes several important principles for precision oncology implementation. The molecular tumor board approach proved essential for treatment selection, enabling clinically relevant decision-making beyond simple mutation-drug matching. The study's tumor-agnostic design successfully identified patients who benefited from targeted therapies regardless of primary tumor histology.
Paolo Marchetti, the study's lead author, and colleagues noted that the trial provides "robust randomized evidence supporting the integration of comprehensive genomic profiling and molecular tumor board-driven decisions into clinical oncology practice."
The findings suggest that precision oncology strategies can meaningfully extend disease control when guided by multidisciplinary expertise. However, the lack of overall survival benefit, attributed to crossover effects, highlights the importance of implementing genomic testing and targeted treatments earlier in the disease course.
Future Directions
The researchers emphasize that these results reinforce the need for broader adoption of genomic profiling and structured MTB integration to optimize outcomes in advanced solid tumors (search). The trial's success in demonstrating clinical benefit across multiple tumor types supports the continued development of tumor-agnostic precision oncology approaches.
The study also underscores the complexity of implementing precision medicine, requiring not just genomic testing but also multidisciplinary expertise to interpret complex molecular data and guide personalized treatment decisions that extend beyond traditional histopathological classifications.