The role of the molecular tumor board: learnings from the ROME trial

Precision Oncology transformed cancer therapy by personalizing treatment based on specific tumor molecular alterations. However, the increasing complexity of genomic and multi-omic data challenges clinical interpretation. Molecular Tumor Boards (MTBs) are critical for integrating expertise and translating genomic profiling into treatment recommendations. The Phase II ROME trial compared personalized therapy, guided by genomic profiling and MTB review, with standard-of-care (SoC) in patients with advanced solid tumors. Between Nov 2020 and Aug 2023, 897 patients were discussed by the MTB, and 400 were randomized. Key drivers for randomization included high TMB, MSI, or actionable alterations, frequently affecting the PIK3CA/AKT/PTEN pathway. Exclusions were mainly due to a lack of actionable alterations or unavailable trial drugs. The ROME trial demonstrates the substantial role of MTBs in interpreting complex molecular data and driving precision oncology, refining patient selection, and optimizing therapy use. The standardization and implementation of MTBs are crucial for improving patient outcomes. The trial is registered on ClinicalTrials.gov with identifier NCT04591431 and in the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) with number 2018-002190-21. The competent authority, Agenzia Italiana del Farmaco (AIFA), authorized the trial on 8 July 2020 (AIFA/SC/P/76132).