Ethics approval and consent to participate
The study was conducted according to the International Conference on Harmonization Good Clinical Practice Guidelines and Declaration of Helsinki and was approved by the institutional ethical review boards of the participating sites and Spanish health authorities. Written informed consent was obtained from all patients before performing any protocol-specific procedures.
Availability of data and material
The datasets used and/or analyzed in our study are available from the corresponding author upon reasonable request.
L. de la Cruz-Merino received consulting or advisory role fees from Merck Sharp & Dohme (MSD)-Merck, Roche, Bristol-Myers-Squibb (BMS), Pierre-Fabre, Amgen, and Novartis; research funding from MSD-Merck, Roche, and Celgene; speaker’s honoraria from MSD-Merck, Roche, BMS, and Amgen; and grant support from Roche and BMS. M Gion received honoraria from Roche and traveled accommodation from Pfizer. J. Cruz received consulting or advisory role fees from Roche, PharmaMar, Lilly, Novartis, Eisai, Pfizer Amgen, and Celgene; travel accommodation from Roche, Novartis, and PharmaMar. V. Quiroga received speakers’ bureau honoraria from Pfizer, Novartis, and Roche; research funding from Celgene; and travel accommodation from Novartis, Roche, and Pfizer. F. Moreno received an advisory role honoraria from Pfizer, Roche, Novartis MSD, and AstraZeneca; speaker’s bureau honoraria and research funding from Pfizer; and travel accommodation from Pfizer, Roche, and Novartis. R. Andrés received travel accommodation from Roche. M. Santisteban received honoraria from Roche, Novartis, and Pfizer; and consulting or advisory role honoraria from Gilead, MSD, Novartis, Pfizer, and Biomerieux. M. Ramos received speakers’ bureau honoraria from Novartis, Roche, and Pfizer. J. Cortés has stock and other ownership interests in MedSIR and has received honoraria from Novartis, Eisai, Celgene, Pfizer, Roche, SAMSUNG, Lilly, MSD, and Daiichi Sankyo; consulting or advisory role honoraria from Celgene, Cellestia Biotech, AstraZeneca, Biothera, Merus, Roche, Seattle Genetics, Daiichi Sankyo, ERYTECH Pharma, Polyphor, Athenex, Lilly, Servier, MSD , GlaxoSmithKline (GSK), Leuko, Clovis Oncology, Bioasis, Boehringer Ingelheim, and Kyowa Kyrin; research funding from ARIAD, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer, Eisai Farmaceutica, Guardanth health, MSD, Pfizer, Puma CO, Queen Mary University of London, Roche, and Piqur; and travel accommodation from Roche, Pfizer, Eisai, Novartis, and Daiichi Sankyo. E. López received consulting or advisory role honoraria from AstraZeneca, Pfizer, Roche, and Novartis; and the speaker’s bureau honoraria from Roche, Eisai, Pfizer, and Novartis. A. Cortés received consulting or advisory role honoraria from Lilly, Roche, Clovis, Ferrer, and Pfizer; speakers’ bureau honoraria from MSD, GSK, AstraZeneca, Roche and Pfizer, and research funding and travel accommodation from Pfizer. L. M. Rodríguez received honoraria from Pfizer and Pierre Fabre. I. Ceballos received consulting or advisory role honoraria from Roche and Merk KGaA; speakers’ bureau honoraria from Roche, Pfizer, BMS, and Celgene; and travel accommodation from Roche, Merck, Pfizer, and Novartis. F. Rojo received consulting or advisory role fees from Roche, AstraZeneca, Novartis, BMS, MSD, Lilly, Pfizer, Genomic Health, Guardant Health, Archer, and Pierre-Fabre; speaker bureau/expert testimony fees from Roche, AstraZeneca, Novartis, BMS, MSD, Lilly, Pfizer, and Pierre-Fabre; and travel accommodation from Roche and Novartis His institution received research grant/funding from Roche and Pfizer. The rest of authors declare no conflict of interest.
The study was partially supported by a research grant from Merck (MSD in Europe) Investigator Initiated Studies Program, which also supplied pembrolizumab.
Conceptualization, L.dC., F.R. and R.C.; Methodology, LdC, F.R., SB, SBe, R.C. and M.Ch.; Software and Validation SB and S.Be.; Formal Analysis, M.C.; Investigation and Data Curation, L.dC., F.R., C.J-C., V.S-M., M.G., J.C., V.Q., R.A., F.M., J.L.A-R., M.R., E.H., J.C., E. L-M., F.H., N.P-C., L.M.R., I.C., M.S., A.C., A.S. and A.P. Resources, L.dC., F.R., C.J-C., V.S-M., M.G., J.C., V.Q., R.A., F.M., J.L.A-R., M.R., E.H., J.C., E. L-M., F.H., N.P-C., L.M.R., I.C., M.S., A.C., A.S., A.P., R.C., M.Ch., S.B and S.Be.; Writing – Original Draft Preparation, L.dC., F.R., S.B., M.C., R.C., M.Ch. and S.Be.; Writing – Review & Editing and Visualization, all authors.; Supervision, L.dC. and S.B.; Project Administration, L.dC., S.B. and S.Be.; Funding Acquisition, L.dC., R.C., and S.B.
We acknowledge the investigators (see list below), pathology departments, and other staff of the participant sites, the patients, and the GEICAM staff involved in this trial. We would like to thank Editage (www.editage.com) for English language editing.