The phase 2 ROME trial, presented at the 2024 ESMO Congress, reveals that targeted treatment based on mutational status significantly improves outcomes in pretreated patients with metastatic solid tumors. The study, which included 400 patients with 38 different tumor types, demonstrated a statistically significant improvement in overall response rate (ORR) and progression-free survival (PFS) compared to standard of care (SOC). These findings suggest a potential paradigm shift in how advanced cancers are managed, moving towards personalized treatment strategies guided by comprehensive genomic profiling.
Study Design and Patient Population
The ROME trial enrolled patients with metastatic disease who had received one to two prior lines of therapy. Participants were randomized 1:1 to either comprehensive genomic profiling via FoundationOne CDx and LiquidCDx followed by molecular tumor board discussion, or to SOC. The most common cancers represented in the trial were colorectal (16%), breast (10%), gastric (9%), glioblastoma (9%), and biliary tract (9%). The molecular tumor board integrated clinical and genomic information to define the most effective and safe therapy or combination strategy.
Key Findings
The trial's results showed a notable improvement in ORR in the targeted treatment arm, with 17.0% compared to 9.5% in the SOC arm (P = .026). The median PFS was 3.7 months in the targeted arm and 2.8 months in the SOC arm (HR 0.64; 95% CI, 0.51-0.80; P < .001). The 12-month PFS rate was 22% in the targeted treatment group versus 7% in the SOC group.
While the median overall survival (OS) was 9.2 months in the targeted therapy group and 7.6 months in the SOC group, this difference was not statistically significant (HR 0.89; 95% CI, 0.68-1.13; P = .299). However, the investigators noted that 52% of patients in the SOC group received targeted therapy during the crossover phase, which may have influenced the OS results.
Role of Genomic Alterations and Targeted Therapies
The most common targetable genomic alterations identified in the study were hTMB (34%), PIK3CA/AKT/PTEN (19%), ERBB2 (14%), FGFR (8%), and microsatellite instability (MSI; 4%). The most frequently prescribed targeted therapies included ipilimumab plus nivolumab (37%), ipatasertib (16%), pemigatinib (8%), T-DM1 (8%), and atezolizumab plus ipatasertib (6%).
Exploratory Analysis in hTMB/MSS Patients
An exploratory analysis focused on patients with hTMB and microsatellite stable (MSS) disease revealed a median PFS of 3.6 months in the targeted therapy group treated with immunotherapy, with a 12-month PFS rate of 32.7%. In contrast, the SOC cohort had a median PFS of 2.8 months and a 12-month PFS rate of 6.3% (HR 0.65; 95% CI, 0.42-0.92; P = .01).
Safety Profile
The rate of grade 3 or higher adverse effects was lower in the targeted treatment arm (35%) compared to the SOC arm (40%), suggesting that targeted therapies, when guided by genomic profiling, can be administered with a manageable safety profile.
Expert Commentary
According to Andrea Botticelli, MD, Department of Medical Oncology at Sapienza Universita di Roma, "The mutational model guided by compressive genomic profiling and molecular tumor board activities could adapt to overcome some limitation of previous models and allow for the selection of more effective targeted therapies."
