Ethics approval and consent to participate: The study was performed in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Approval for the study protocol and all accompanying material provided to patients was obtained from independent ethics committees at participating institutions. All patients provided written informed consent.
Consent for publication: N/A.
Availability of data and materials: Qualified researchers may request access to individual patient level data through the clinical study data request platform (https://vivli.org/). Further details on Roche's criteria for eligible studies are available here: https://vivli.org/members/ourmembers/. For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here: https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm>
Competing Interests: All authors received support for third-party writing assistance for this manuscript, provided by F. Hoffmann-La Roche Ltd. Professor Kümmel has received consulting fees from F. Hoffmann-La Roche Ltd, Genomic Health, Novartis, Amgen, Celgene, Daiichi Sankyo, AstraZeneca, Somatex, Merck Sharp & Dohme, Pfizer, Puma Biotechnology, and PFM Medical, and has received non-financial support outside the submitted work for a travel grant from F. Hoffmann-La Roche Ltd, Daiichi Sankyo, and SonoScape. Dr. Tondini has received an institutional grant from ASST PAPA GIOVANNI XXIII for participation in the MetaPHER study, and institutional grants for participation in other clinical trials from F. Hoffmann-La Roche Ltd, Novartis, Merck Sharp & Dohme, Bristol-Myers Squibb, AstraZeneca, and Array BioPharma, Inc. Dr. Abraham has received personal fees for conference participation from Eisai, and personal fees for an advisory board from Merck & Co, Inc. Dr. Nowecki has received a travel grant from F. Hoffmann-La Roche Ltd. Dr. Itrych has no other conflicts to disclose. Dr. Hitre has received research funding and non-financial support (i.e. drugs) outside the submitted work from F. Hoffmann-La Roche Ltd. Dr. Karaszewska has received research grants from F. Hoffmann-La Roche Ltd, Novartis, Merck & Co, Inc., and Amgen. Dr. Juárez-Ramiro has received fees for clinical research from F. Hoffmann-La Roche Ltd, Bristol-Myers Squibb, Merck Sharp & Dohme, Bayer, Pfizer, and Amgen, and personal speaker fees from F. Hoffmann-La Roche Ltd, Bristol-Myers Squibb, Merck Serono, Bayer, and Amgen. Dr. Morales-Vásquez has received consulting fees from F. Hoffmann-La Roche Ltd, AstraZeneca, and Asofarma. Dr. Pérez García has received personal fees for an advisory board and travel grants from F. Hoffmann-La Roche Ltd, and has received personal fees for an advisory board from Lilly. Dr. Cardona-Huerta has received consulting fees from F. Hoffmann-La Roche Ltd and AstraZeneca. Dr. Monturus is an employee of F. Hoffmann-La Roche Ltd (author and spouse/partner) and has stock/ownership interest in F. Hoffmann-La Roche Ltd/Genentech, Inc. (author and spouse/partner). Dr. Sequi is an employee of Parexel and is contracted by F. Hoffmann-La Roche Ltd. Dr. Restuccia is an employee of F. Hoffmann-La Roche Ltd and has stock/ownership interest in F. Hoffmann-La Roche Ltd. Dr Benyunes is an employee of Genentech, Inc. Dr. Martín has received research grants and personal fees from F. Hoffmann-La Roche Ltd, PUMA, and Novartis, consulting/advisory fees from AstraZeneca, Amgen, Taiho Oncology, F. Hoffmann-La Roche Ltd/Genentech, Novartis, PharmaMar, Eli Lilly, PUMA, Daiichi Sankyo, and Pfizer.
Funding: This study was sponsored by F. Hoffmann-La Roche Ltd.
Author Contributions: All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Kümmel, Tondini, Abraham, Karaszewska, Juárez-Ramiro, Cardona-Huerta, Monturus, Sequi, Restuccia
Acquisition, analysis, or interpretation of data: Kümmel, Tondini, Abraham, Nowecki, Hitre, Karaszewska, Juárez-Ramiro, Morales-Vásquez, Pérez García, Cardona-Huerta, Monturus, Sequi, Restuccia, Benyunes, Martín
Drafting of the manuscript: Kümmel, Cardona-Huerta, Monturus, Restuccia, Martín
Critical revision of the manuscript for important intellectual content: All authors
Statistical analysis/Quality control of data and algorithms: Karaszewska, Pérez García, Sequi, Martín
Acknowledgments: The sponsor, F. Hoffmann-La Roche Ltd., contributed to the design of this study. Data collected by the investigators were analyzed by statisticians at F. Hoffmann-La Roche Ltd. Authors employed by the study sponsor contributed to the conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript, as well as the decision to submit the manuscript for publication. We would also like to thank all volunteers, patients, and other investigators who participated in this study. Support for third-party writing assistance for this manuscript, furnished by Katie Wilson, PhD, and Stephen Salem, BSc, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland.