Andrea Botticelli, MD, PhD, Sapienza University, Rome, Italy, discusses final results from the phase 2 ROME trial which demonstrated that using comprehensive genome profiling to guide treatment can improve response and survival among pretreated patients with metastatic solid tumors. 

Dr Botticelli presented these results at the 2024 European Society of Medical Oncology (ESMO) Congress in Barcelona, Spain. 

Transcript: 

Hi, I am Andrea Botticelli, I am a researcher and oncologist, a professor at Sapienza University of Rome, and the Director of Breast Unit at Umberto University of Rome. We are going to present the final results of the ROME trial. 

The ROME trial is a phase 2 trial which aims to demonstrate if a diagnostic approach is really superior to standard of care. The ROME trial is a phase 2, multicenter, multi-basket, randomized trial that enrolled patients affected by solid tumors, regardless of histology, who had to receive at least 1 line of previous therapy, but no more than 2 lines of previous therapy. All of these patients were screened with comprehensive genomic profiling both on tissue and liquid biopsy, and once molecular alteration that could be targeted with a drug available in an interim trial was identified, the clinical case was discussed in the Molecular Tumor Board, they play a crucial role in the ROME trial. The Molecular Tumor Board decided whether to enroll patients and proceed with randomization or to consider patients screening failure. 

The patients enrolled were randomized to receive 1-to-1 targeted therapy according to the mutational profile and decided by the Molecular Tumor Board, or standard of care decided by the investigators but shared with the Molecular Tumor Board. The primary end point of the study was objective response rate and the secondary end points were progression-free survival, overall survival, the safety profile, time to next treatment, and time to treatment failure. We also had several exploratory end points such as the progression-free survival of targeted therapy versus standard of care in the homogeneous group of patients. 

From November 2020 to August 2023, 1,794 patients were screened and of them 897 patients presented with alterations, so almost 55% of patients, and these patients were discussed in the Molecular Tumor Board and 400 patients were enrolled. The most frequent alterations that we have found in the ROME trial were high tumor mutational burden in 34% of patients, alteration of the PIK3CA pathway in 25% of patients, alteration of ERBB2/HER2 in 14% of patients, alteration of FGFR in 8% of patients and MSI. The most frequent drugs proposed by the Molecular Tumor Board were ipilimumab plus nivolumab followed by ipatasertib, T-DM1(trastuzumab emtansine), and pemigatinib. 

The primary end point of the ROME trial was objective response rate, and the ROME trial met its primary end point with objective response rate in the [targeted therapy] arm was 17% vs 9.5%. In particular, we achieved 2.5% of patients in the [targeted therapy] complete response. Targeted therapy demonstrated also an improvement in progression-free survival with a PFS rate at 1-year of 22% in [targeted therapy] arm versus 7% in standard of care. Unfortunately, the targeted therapy didn't demonstrate an improvement in overall survival, even though crossover was planned and 52% of patients in standard of care received targeted therapy in the crossover phase. The toxicity profile was similar in terms of severe toxicity in standard of care and in targeted therapy.

The steering committee decided also to present at ESMO the data about a homogeneous group of patients characterized by high tumor mutational burden. This data is really interesting because the PFS rate in the high tumor mutational burden and MSI was 57% at 1 year versus 0, and in this group of patients without high tumor mutational burden and MSI was 32% versus 6%. 

In conclusion, in metastatic patients affected by solid tumors regardless of histology, targeted therapy driven by comprehensive genomic profiling and Molecular Tumor Board activity could really improve progression-free survival, objective response rate, even though the overall survival was not superior due to the crossover phase. This is a normal landscape of treatment of cancer in which a genomically-driven strategy really needs to be driven by the Molecular Tumor Board. 

Source: 

Botticelli A, Scagnoli S, Conte Pierfranco, et al. The Rome trial from histology to target: The road to personalize targeted therapy and immunotherapy. Presented at 2024 ESMO Congress. September 13-17, 2024. Abstract LBA7