Abstract
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).
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Data availability
Individual deidentified participant data generated during the current study are available upon reasonable request from academic or qualified clinical researchers affiliated with recognized institutions, strictly for the purpose of conducting non-commercial, ethically approvable research aligned with the original scope of the trial. Applicants are required to submit a detailed research proposal, curriculum vitae, and a declaration of non-conflict of interest. Requests must clearly describe the research objectives and methodology and must be reviewed and approved by the steering committee of the ROME trial during dedicated review sessions. Approval is granted based on scientific merit, data availability, intended data use, and absence of overlapping research initiatives by the trial investigators. All approved requestors will be required to sign a data access agreement that restricts data use solely to the approved research project and prohibits any further distribution or use. Data will be shared via a secure data-sharing platform within 4–8 weeks of approval, contingent upon data volume and complexity. Data requests will be considered within 12 months of manuscript publication. The trial registration, study protocol, and methodological details are publicly accessible through ClinicalTrials.gov (accession identifier NCT04591431). Additional publicly available datasets used in the analysis include the ClinVar database: freely accessible at https://www.ncbi.nlm.nih.gov/clinvar/; the OncoKB database: accessible at https://www.oncokb.org/; the COSMIC database: accessible at https://cancer.sanger.ac.uk/cosmic; and the ESMO ESCAT scale: accessible at https://www.esmo.org/guidelines/esmo-scale-for-clinical-actionability-of-molecular-targets-escat. No other public repositories or datasets requiring accession codes were used in this study.
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Acknowledgements
The authors would like to thank P. Bruzzi, former Director of the Complex Structure at the National Institute for Cancer Research in Genoa and University Professor, for his valuable comments and advice, which helped enhance the clarity, readability, and comprehensibility of the methodological and statistical aspects of this work. The authors would also like to express their gratitude to the members of the Data and Safety Monitoring Committee, Dr. Fausto Petrelli (ASST Bergamo Ovest, Medical Oncology Unit, Treviglio), Dr. Eliana Rulli (Mario Negri Institute, Milan), and Prof. Roberto Labianca (formerly at Ospedali Riuniti di Bergamo), for their invaluable oversight and guidance throughout the study. Erlotinib, pertuzumab, vemurafenib, trastuzumab emtansine, alectinib, vismodegib, cobimetinib, atezolizumab, trastuzumab, ipatasertib (GDC-0068), entrectinib and pralsetinib were provided by Roche; everolimus, lapatinib and alpelisib were provided by Novartis; palbociclib and talazoparib were provided by Pfizer; ipilimumab and nivolumab were provided by Bristol Myers Squibb; brigatinib was provided by Takeda; ponatinib and itacitinib (INCB039110) and pemigatinib (INCB054828) were provided by Incyte; selpercatinib was provided by Eli Lilly; and tepotinib was provided by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945). NGS tests FoundationOne CDx and FoundationOne Liquid CDx were provided by Foundation Medicine, Inc. This study was supported through unrestricted grants provided by Roche, Takeda, Bristol Myers Squibb, Pfizer, Incyte, and Eli Lilly. These contributions were regulated by contractual agreements with the study sponsor: the Fondazione per la Medicina Personalizzata (FMP). The funding entities had no role in study design, data collection, analysis, interpretation, or manuscript preparation. Generative artificial intelligence (AI-Perplexity) tools were used during the drafting process exclusively to refine language and improve readability. All data collection, analysis, and interpretation were carried out by the Authors. The Authors assume full responsibility for the scientific content, and all text generated with AI support was carefully reviewed, edited, and approved by the Authors prior to submission.
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Conceptualization: P.M. and A.B. Patient enrollment and investigation: G.C., M.B., S.L., S.S., L.F., V.G., U.D.G., P.A., M.A., C.C., P.C., S.S. E. Crimini, S.P., S.V., F.D.G., R. Bordonaro, S.B., G. Butturini, L.D.M., A.D.C., A.F., E.F., S.G., G.M., A.P., D.P., F.P., S.T., A.Z., D.M., F.C., F.M., G.T., A.B., A.S., V.A., D.Q., P.T., P.D., B.U., C.B., E.Z., C.P., A.T., L.B., E.M., C.M., A.R. and R. Berardi. MTB: P.M., G.C., M.B., S.S., P.A., G. Blandino., G.D., M.A., C.C., P.C., E. Capoluongo, F.C., B.C., G.G., U.M., F.M., M.N., G.P., L.S. and A.B. Methodology: L.S., M.C., P.M., A.B., S.S., M.B., P.A., G. Blandino, G.D., M.A., C.C., P.C., E. Capoluongo, F.C., B.C., G.G., U.M., F.M., M.N., G.P., N.M. and M.S. Software: M.C. and L.S. Formal analysis and data curation: M.C. and L.S. Validation: P.M., A.B., S.V., L.S. and M.C. Writing—original draft preparation: P.M., G.C., S.S., E. Crimini, S.P., S.V., C.B.W. and A.B. Writing—review and editing: all authors. Visualization: P.M., S.V., S.S., E. Crimini, M.C., and A.B. All authors read and agreed to this version of the manuscript.
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P.M. had a consultant/advisory role for Bristol Myers Squibb, Roche Genentech, Merck Sharp & Dohme, Novartis, AMGEN, Merck Serono, Pierre Fabre, and Incyte. He is a member of the advisory board of Drug-PIN. A.G. is the holder of patent PTC/IB2019/052310. G.C. had a role in advisory board for Roche, AstraZeneca, Daiichi Sankyo, Eli Lilly, Novartis, Pfizer, Gilead, Menarini, Exact Sciences, Bristol Myers Squibb, and Merck. C.B.W. served as an advisor for: AstraZeneca, BMS, Frankfurt Institute of Clinical Cancer Research (IKF), Incyte, Johnson & Johnson, Roche, Taiho. He received honoraria from Amgen, AstraZeneca, Bayer, BMS, GSK, Johnson & Johnson, Lilly, MSD, Merck, Pierre Fabre, QuIP GmbH, Roche, Servier; received travel support from Bayer, Johnson & Johnson, Roche, Servier, Taiho, and research funding from Roche (institutional). He serves as serves as faculty for European Society of Medical Oncology (ESMO), Deutsche Krebshilfe (DKH), and Arbeitsgemeinschaft internistische Onkologie (AIO), is a member of the EU Commission expert group: Mission Board for cancer, and of the BMBF steering committee: Strategiekreis Dekade gegen Krebs. M.B. is employed in the Italian National Institute of Health (Istituto Superiore di Sanità) and is an unpaid member of the Technical and Scientific Committee of the Italian Medicine Agency (AIFA). S.L. was an invited speaker for Amgen, AstraZeneca, Bristol Myers Squibb, Incyte, GlaxoSmithKline, Eli Lilly, Merck Serono, Merck Sharp & Dohme, Pierre Fabre, Roche and Servier and had a role in advisory boards for Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Incyte, Eli Lilly, Merck Serono, Merck Sharp & Dohme, Servier, Takeda, Rottapharm, BeiGene, Fosun Pharma and Nimbus Therapeutics. S.S. was an invited speaker for Pfizer, Eli Lilly, Novartis, Daiichi Sankyo, Gilead, Roche, and AstraZeneca. L.F. reports speaking honoraria from Incyte, Bristol Myers Squibb, and Eli Lilly. He also received institutional research funding from Merck Sharp & Dohme, Bristol Myers Squibb, AstraZeneca, Incyte, BeiGene, Astellas, Daiichi Sankyo, and Roche. He had a role in advisory boards for Merck Sharp & Dohme, AstraZeneca, Incyte, Taiho, Servier, Daiichi Sankyo, Eli Lilly, and Astellas. V.G. has a role in leadership for AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, Gilead, Merck Sharp & Dohme, Novartis, Pfizer, Olema Oncology, Pierre Fabre, and Menarini Stemline. She had a role as a speaker for AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, Gilead, GlaxoSmithKline, Novartis, Roche, Zentiva, Menarini Stemline, and provided expert testimony for Eli Lilly. U.D.G. received consultation fees from Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Esai, Ipsen, Johnson & Johnson Innovative Medicine (formerly Janssen), Merck KGaA, Merck Sharp & Dohme, Novartis, and Pfizer, and travel expenses for attending symposia from AstraZeneca, Ipsen, and Pfizer. P.A., G.B., G.D., M.A., C.C., P.C., E. Crimini, and M.C. declare no competing interests. S.P. had a role as consultant/advisor for AstraZeneca, Eli Lilly, Daiichi Sankyo, Novartis, Pfizer, Seagen, Sophos, and Gilead and received travel and accommodation fees from Daiichi Sankyo, Pfizer, AstraZeneca, Eli Lilly, Menarini, Novartis, and Gilead. S.V. had a role as a speaker for Novartis. R.B. declares no competing interests. S.B. received congress travel support from Merck Sharp & Dohme, Pfizer, Bayer, and Ipsen and had a role in advisory boards and steering committees for Pfizer, Bristol Myers Squibb, Merck Sharp & Dohme, Astellas, Roche, Johnson & Johnson, Ipsen, Bayer, Novartis, Merck, AstraZeneca, and Gilead. G.B. declares no competing interests. L.D.M. received personal grant for advisory/consultant/speaker activities from Agendia, AstraZeneca, Daiichi Sankyo, Eli Lilly, Eisai, Exact Sciences, Gilead, GlaxoSmithKline, Ipsen, Roche, Seagen, Menarini, Stemline, Merck Sharp & Dohme, Novartis, Olema, Pierre Fabre, and Pfizer. A.D.C. declares no competing interests. A.F. received financial fees from Roche, Menarini, Pfizer, Eli Lilly, Novartis, Daiichi Sankyo, AstraZeneca, and Gentili. F.DG had consulting fees with Novartis, BMS, MSD, and Pierre-Fabre. E.F., S.G., G.M., A.P., and D.P. declare no competing interests. F.P. received honoraria for advisory boards, activities as a speaker, travel grants, and research grants from Amgen, AstraZeneca, Daiichi Sankyo, Celgene, Eisai, Eli Lilly, Exact Sciences, Gilead, Ipsen, Italfarmaco, Menarini, Merck Sharp & Dohme, Novartis, Pierre Fabre, Pfizer, Roche, Seagen, Takeda, and Viatris. He received research funding from AstraZeneca, Eisai, and Roche. S.T. declares no competing interests. A.Z. received honoraria for consultancy and advisory board from Roche, Novartis, Eli Lilly, AstraZeneca, Pfizer, Exact Sciences, Merck, Daiichi Sankyo, Gilead, Seagen, Menarini, and Stemline. D.M. had a role in advisory boards for Roche, Merck Sharp & Dohme, Merck, and AstraZeneca, and received fees for travel and meetings from Pierre Fabre and Amgen. F.C. received fees for membership of an advisory board or lectures from Roche, AstraZeneca, Bristol Myers Squibb, Pfizer, Takeda, Eli Lilly, Bayer, Amgen, Sanofi, Pharmamar, Novocure, Mirati, Galecto, OSE, Illumina, Thermo Fisher Scientific, BeiGene, and Merck Sharp & Dohme. B.C. had a role in advisory boards for Merck Sharp & Dohme and Daiichi Sankyo. G.G. declares no competing interests. U.M. has received personal fees (as a consultant and/or speaker bureau) from Boehringer Ingelheim, Roche, Merck Sharp & Dohme, Amgen, Thermo Fisher Scientific, Eli Lilly, Diaceutics, GlaxoSmithKline, Merck, AstraZeneca, Janssen, Diatech, Novartis, and Hedera. F.M. and M.N. declare no competing interests. G.P. received financial fees from Illumina, Roche, Eli Lilly, AstraZeneca, Exact Sciences, and ADS Biotech. M.S. and L.S. declare no competing interests. G.T. had a role in advisory boards for Molteni, Novartis, PharmaMar, and Merck Sharp & Dohme. A.S., V.A., D.Q., P.T., P.D., B.U., C.B., and E.Z. declare no competing interests. C.P. received personal fees for advisory role, speaker engagements, and travel accommodation expenses from Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Eisai, Ipsen, Janssen, Incyte, Merck Serono, Merck Sharp & Dohme, Novartis, Roche, Sandoz, Sanofi, and Servier. A.T., L.B., E.M., C.M., and A.R. declare no competing interests. R. Berardi received consulting fees and/or donations to institution from AstraZeneca, Pfizer, Roche, Astellas, Eisai, Merck Sharp & Dohme, Menarini, Gilead, Pierre Fabre, Bristol Myers Squibb, Seagen, Incyte, Eli Lilly, Bayer, and Daiichi Sankyo. G.L. received advisory/consulting fees from AbbVie, Bayer, Novartis, Orbus, Celgene, GlaxoSmithKline, Health4u, Braun Melsungen, Janssen, BioRegio-Stern, Servier, Novocure, and TME Pharma and travel fees from Roche, Bayer, and Servier. A. Piancastelli declares no competing interests. G. Masi received fees for advisory boards from AstraZeneca, Bayer, Ipsen, Merck Sharp & Dohme, Eisai, Roche and Sirtex; speaking honoraria from Amgen, AstraZeneca, Roche, Merck Sharp & Dohme, Eisai, Terumo and Sirtex; travel grants from AstraZeneca, Bayer, Ipsen, Merck Sharp & Dohme, Eisai and Roche; and research grants from Roche, Terumo and Sirtex. L.B., V.V., and F. Mannozzi declare no competing interests. N.M. received advisory board consultation fees from Roche, Daiichi Sankyo, Pfizer, and AstraZeneca. A.B. had a role in advisory boards and steering committees and has been an invited speaker for Novartis, Roche, Eli Lilly, Pfizer, AstraZeneca, Daiichi Sankyo, Gilead, Merck Sharp & Dohme, Bristol Myers Squibb, and Gentili.
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Marchetti, P., Curigliano, G., Westphalen, C.B. et al. The role of the molecular tumor board: learnings from the ROME trial. npj Precis. Onc. (2026). https://doi.org/10.1038/s41698-026-01386-1
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DOI: https://doi.org/10.1038/s41698-026-01386-1
