Funding

No external funding was used in the preparation of this manuscript.

Conflicts of Interest

Ondřej Fiala received honoraria from Roche, Janssen, GSK, and Pfizer for consultations and lectures unrelated to this project. Francesco Massari has received research support and/or honoraria from Advanced Accelerator Applications, Astellas, Astra Zeneca, Bayer, BMS, Janssen, Ipsen, MSD, and Pfizer outside the submitted work. Umberto Basso received honoraria for Bristol-Myers Squibb, Novartis, and Astra Zeneca; research funding from Ipsen; and travel grants from Bristol-Myers Squibb, Janssen Oncology, Astellas Pharma, MSD Oncology, Merck/Pfizer, and Bayer, all unrelated to this project. Sebastiano Buti received honoraria as speaker at scientific events and advisory role by BMS, Pfizer, MSD, Ipsen, Roche, Eli Lilly, AstraZeneca, Pierre-Fabre, Novartis, Merck, Gentili, and Astellas, all unrelated to the present paper. Yüksel Ürün has served on advisory board for Abdi-İbrahim, Astellas, AstraZeneca, Bristol Myers-Squibb, Deva, Eczacıbaşı, Gen ilaç, Gilead, GSK, Janssen, Merck, MSD, Novartis, Pfizer, and Roche and received travel grants, honoraria, or consultation fees from Abdi-İbrahim, Astellas, Bristol Myers-Squibb, Deva, Eczacıbaşı, Gen İlaç, Gilead, GSK, Janssen, Merck, Novartis, Pfizer, and Roche, all unrelated to the present paper. Maria T. Bourlon is a consultant of Bristol Myers Squibb, Merck, MSD, Gilead, Astellas, and Asofarma and a speaker for Janssen Pharmaceuticasl, MSD, Merck, and Astellas, all unrelated to the present paper. Mimma Rizzo has received honoraria as a speaker/consultant by MSD, Merck Serono, Astrazeneca, Bristol Myers Squibb, Eisai, and Gilead, all unrelated to the present paper. Linda Cerbone has received honoraria for advisory boards, speaker engagements, and scientific consultancy for educational purposes from AstraZeneca, EISAI, MSD, Ipsen, BMS, and A.A.A.; and is a past MSD employee in Medical Affairs. Javier Molina-Cerrillo reports research funding from Roche, Ipsen, Pfizer, and Janssen; travel support from Pfizer, Janssen, Ipsen, and BMS; and a consulting or advisory role with Ipsen, Roche, BMS, Pfizer, Sanofi, Janssen, Astellas, Eisai, Adium, and MSD, all unrelated to the present paper. Álvaro Pinto is a member of advisory boards of Pfizer, Novartis, Ipsen, BMS, Janssen, Astellas, Sanofi, Bayer, Clovis, Roche, MSD, Pierre Fabre, and Merck; has received research support from Pfizer and BMS; clinical trial payments from Pfizer, Bayer, Janssen, MSD, Clovis, Pharmacyclics, BMS, Sanofi, Astra Zeneca, Roche, Eisai, and Aveo; and travel arrangements from Janssen, Roche, Pfizer, BMS, and Ipsen, all unrelated to the present paper. Andrey Soares reports honoraria from Janssen, Pfizer, Bayer, AstraZeneca, Astellas Pharma, Merck Serono, Sanofi, Ipsen, and Adium; consulting or advisory role from Astellas Pharma, Janssen, Roche, Bayer, AstraZeneca, MSD, Bristol-Myers Squibb, Adium, Ipsen, Pfizer, and Novartis; research funding from Bristol-Myers Squibb (Inst), Astellas (Inst), and AstraZeneca (Inst); travel, accommodations, and expenses from Bayer, Janssen, Ipsen, Adium, MSD, and Merck Serono; and ownership in BIO, Brazilian Information Oncology; all unrelated to this study. Alexandr Poprach has received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from BMS, Ipsen, Roche, Astellas, Merck, Eisai, MSD, Novartis, and Pfizer, unrelated to this project. Gian Paolo Spinelli has received payment or honoraria for advidory boards from Novartis, Roche, and Bayer, unrelated to this project. Martin Angel received honoraria from Roche, Johnson & Johnson, Raffo, and Pfizer for consultations and lectures unrelated to this project. Fernando Sabino M. Monteiro reports research support provided by Merck Sharp Dome; honoraria from Janssen, Ipsen, Bristol Myers Squibb, and Merck Sharp Dome; and ownership in BIO, Brazilian Information Oncology, all unrelated to this study. Camillo Porta acted as a remunerated consultant and/or speaker for Angelini Pharma, AstraZeneca, BMC, Eisai, Exilixis, Genenta, Ipsen, Merck Serono, and MSD; as a protocol steering committee member for Eisai and MSD; and as an Independent Review Board member for Genenta. Shilpa Gupta is a consultant for Bristol Myers Squibb, Merck, Pfizer, Gilead, Bayer, and Seattle Genetics; is a speaker for Bristol Myers Squibb; and has institutional research funding from Seatte Genetics, Pfizer, Merck, Bristol Myers Squibb, Roche, Novartis, and Tyra Biosciences. Matteo Santoni has received research support and honoraria from Janssen, Bristol Myers Squibb, Ipsen, MSD, Astellas, and Bayer, all unrelated to the present paper. Patrizia Giannatempo, Enrique Grande, Zin W. Myint, Ugo De Giorgi, Renate Pichler, Francesco Grillone, Fabio Calabrò, Luca Galli, Ravindran Kanesvaran, Giandomenico Roviello, Jakub Kucharz, Se Hoon Park, Emmanuel Seront, Carlo Messina, Daniele Santini, Akihiro Yano, Lorena Incorvaia, Martina Catalano, Luigi Formisano, Gaetano Facchini, Giuseppe Fornarini, Sara Elena Rebuzzi, Cecilia Nasso, Marco Stellato, Deniz Tural, Gaetano Aurilio, Ilana Epstein, Francesco Carrozza, Giovanni Benedetti, Tomáš Büchler, Cinzia Ortega, Roubini Zakopoulou, Nicola Battelli, and Joaquin Bellmunt declare that they have no conflicts of interest that might be relevant to the contents of this manuscript. Tomáš Büchler and Camillo Porta are Editorial Board members of Targeted Oncology. Tomáš Büchler and Camillo Porta were not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions.

Ethics Approval

The study protocol was approved on 28 September 2023, by the Ethical Committee of the coordinating center (Marche Region – Italy – no. 2022 39/7875, Study Protocol “ARON 2 Study” NCT05290038) and by the Institutional Review Boards of participating centers.

Consent to Participate

Informed consent with subsequent analysis of the follow-up data was obtained from all participants.

Consent for Publication

Not applicable.

Availability of Data and Material

The datasets generated and/or analyzed during the current study are not publicly available due to patient data security but are available from the corresponding author on reasonable request.

Code Availability

Not applicable.

Author Contributions

Study concept and design: all authors; acquisition of data: all authors; analysis and interpretation of data: all authors; drafting of the manuscript: Fiala, Massari, Gupta, and Santoni; critical revision of the manuscript for important intellectual content: all authors; statistical analysis: Santoni; obtaining funding: none; administrative, technical, or material support: none; and supervision: Gupta and Santoni.