Genomically matched therapy in advanced solid tumors: the randomized phase 2 ROME trial

Despite recent advancements demonstrating the potential of tumor-agnostic biomarkers to guide effective therapies, randomized evidence supporting the clinical superiority of precision oncology approaches compared to standard therapies remains limited. The ROME trial was a multicenter, randomized, open-label phase 2 study comparing tailored treatment (TT) to standard of care (SoC) in patients with advanced solid tumors progressing after one or two lines of therapy. Comprehensive genomic profiling on tissue and blood was performed to identify actionable alterations. Overall response rate (ORR) was the primary endpoint, and progression-free survival (PFS), overall survival (OS), time to treatment failure (TTF), time to next treatment (TTNT) and safety were the secondary endpoints. Between November 2020 and August 2023, 1,794 patients were screened, 897 were evaluated by the molecular tumor board (MTB) and 400 were randomized to TT or SoC. TT achieved a significantly higher ORR (17.5% versus 10%; P = 0.0294) and improved median PFS (3.5 months versus 2.8 months; hazard ratio = 0.66 (0.53-0.82), P = 0.0002). TT also showed superior 12-month PFS rates (22.0% versus 8.3%). Median OS was similar, with a 52% crossover rate. Grade 3/4 adverse events were also similar (40% TT versus 52% SoC). These results highlight the potential of TT to improve outcomes for patients with diverse actionable genomic alterations. These results also provide relevant evidence supporting a tumor-agnostic precision oncology strategy and highlight the potential of TTs, guided by genomic profiling and MTB recommendations, to significantly improve outcomes for patients with diverse actionable genomic alterations. ClinicalTrials.gov identifier: NCT04591431 .

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Publication Details

Journal
Nature Medicine
Published
2025-09-29
DOI
https://doi.org/10.1038/s41591-025-03918-x
Citations
14
Primary Topic
Cancer Genomics and Diagnostics
Type
article
Field-Weighted Citation Impact
13.11

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article

Genomically matched therapy in advanced solid tumors: the randomized phase 2 ROME trial

Federico Cappuzzo, Elena Zaffignani, Giuseppe Curigliano, Stefano Tamberi et al.
14 citations
Nature Medicine
Cancer Genomics and Diagnostics
13.11
article

Genomically matched therapy in advanced solid tumors: the randomized phase 2 ROME trial

Federico Cappuzzo, Elena Zaffignani, Giuseppe Curigliano, Stefano Tamberi, Roberto Bordonaro, Mauro Biffoni, Claudia Mucciarini, Fabio Puglisi, Giuseppe Giannini, Elisabetta Fenocchio, Federica Mazzuca, Benedetta Urbini, Rossana Berardi, Bruna Cerbelli, Agnese Fabbri, Stefania Gori, Simona Pisegna, Paolo A. Ascierto, Alberto Zambelli, Giuseppe Lombardi, Valentina Guarneri, Giulio Metro, Pierfranco Conté, Andrea Botticelli, Maurizio Simmaco, Simone Scagnoli, Lorenzo Fornaro, Carmine Pinto, Edoardo Crimini, Paolo Marchetti, Francesca Mannozzi, Evaristo Maiello, Giovanni Blandino, Donatella Marino, Sara Lonardi, Maurizio Ceracchi, Daniele Pozzessere, Vito Vanella, Massimo Aglietta, Giulia d’Amati, Gianluca Masi, Giuseppe Tonini, Sergio Bracarda, Alessandra Piancastelli, Laura Bonanno, Sofia Verkhovskaia, Andrea DeCensi, Ugo De Giorgi, Giancarlo Pruneri, Lucia Del Mastro, Carmelo Bengala, Annamaria Pessino, Chiara Cremolini, L Buffoni, Lidia Strigari, Antonella Savarese, Davide Quaresmini, Pierosandro Tagliaferri, Giovanni Butturini, Ettore Capoluongo, Alicia Tosoni, Marianna Nuti, Vincenzo Adamo, Umberto Malapelle, Nello Martini, P. Damiano, Antonio Russo
article en
14 citations

Abstract

Despite recent advancements demonstrating the potential of tumor-agnostic biomarkers to guide effective therapies, randomized evidence supporting the clinical superiority of precision oncology approaches compared to standard therapies remains limited. The ROME trial was a multicenter, randomized, open-label phase 2 study comparing tailored treatment (TT) to standard of care (SoC) in patients with advanced solid tumors progressing after one or two lines of therapy. Comprehensive genomic profiling on tissue and blood was performed to identify actionable alterations. Overall response rate (ORR) was the primary endpoint, and progression-free survival (PFS), overall survival (OS), time to treatment failure (TTF), time to next treatment (TTNT) and safety were the secondary endpoints. Between November 2020 and August 2023, 1,794 patients were screened, 897 were evaluated by the molecular tumor board (MTB) and 400 were randomized to TT or SoC. TT achieved a significantly higher ORR (17.5% versus 10%; P = 0.0294) and improved median PFS (3.5 months versus 2.8 months; hazard ratio = 0.66 (0.53-0.82), P = 0.0002). TT also showed superior 12-month PFS rates (22.0% versus 8.3%). Median OS was similar, with a 52% crossover rate. Grade 3/4 adverse events were also similar (40% TT versus 52% SoC). These results highlight the potential of TT to improve outcomes for patients with diverse actionable genomic alterations. These results also provide relevant evidence supporting a tumor-agnostic precision oncology strategy and highlight the potential of TTs, guided by genomic profiling and MTB recommendations, to significantly improve outcomes for patients with diverse actionable genomic alterations. ClinicalTrials.gov identifier: NCT04591431 .

Nature MedicineVol. 31(10)
University of Pisa (IT), Marche Polytechnic University (IT), University of Udine (IT), Istituto Nazionale di Statistica (IT), University of Padua (IT), Università Campus Bio-Medico (IT), University of Milan (IT), University of Ferrara (IT), University of Perugia (IT), Casa Sollievo della Sofferenza (IT), Fondazione Roma (IT), Policlinico Umberto I (IT), Ente Ospedaliero Ospedali Galliera (IT), Magna Graecia University (IT), Ospedale Santa Chiara (IT), Azienda Unita' Sanitaria Locale Di Modena (IT), Azienda Sanitaria Unità Locale di Reggio Emilia (IT), Ospedale "Santa Maria delle Croci" di Ravenna (IT), Istituto Ramazzini (IT), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IT), Ospedale Sacro Cuore Don Calabria (IT), Ospedale Garibaldi (IT), Ospedale Papa Giovanni XXIII (IT), Casa di Cura Villa Garda (IT), Istituto Oncologico Veneto (IT), Ospedale Humanitas Gradenigo (IT), Azienda USL di Bologna (IT), Azienda Ospedaliera S.Maria (IT), Istituto delle Scienze Neurologiche di Bologna (IT), Azienda Ospedaliera Sant'Andrea (IT), Ospedale di Belcolle (IT), Centro di Riferimento Oncologico (IT), A. O. Ordine Mauriziano di Torino (IT), Faculdade São Leopoldo Mandic (BR), IRCCS San Camillo Hospital (IT), Istituto Tumori Bari (IT), Ambiente Risorse Sviluppo (IT), Guglielmo da Saliceto Hospital (IT), Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" (IT), Campus Bio Medico University Hospital (IT), Tumori Foundation (US), Ospedale Policlinico San Martino (IT), Candiolo Cancer Institute (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Istituto Pasteur (IT), Ospedale di Prato Santo Stefano (IT), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), Azienda Ospedaliera Universitaria Pisana (IT), Azienda Ospedaliera Ospedali Riuniti Papardo Piemonte (IT), European Institute of Oncology (IT), University of Milano-Bicocca (IT), University of Naples Federico II (IT), University of Genoa (IT), Sapienza University of Rome (IT), University of Palermo (IT)
Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Merck KGaA, Incyte, Foundation Medicine
Openalex Percentile: Top 1%
Cancer Genomics and Diagnostics
13.11
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