title: Moving towards a customized approach for drug development: lessons from clinical trials with immune checkpoint inhibitors in lung cancer.
abstract: Lung cancer has recently been discovered to be an immunological targetable disease, on the basis of the exciting results of the randomized trials with immune checkpoint inhibitors. Nevertheless, the survival benefit appears to not be entirely captured by the usual outcome measures, thus requiring a deep reflection about the appropriateness of the traditional statistical methodologies in this context. The intrinsic biological differences existing both in terms of mechanism of action and kinetic between immunotherapy and chemotherapy or targeted therapy, impact on patients' outcome, requiring a global revolution in the way to design clinical studies with the ideal aim to evolve towards trials carefully 'customized' on the basis of the investigational drug, the specific disease and the biological background. The exciting data recently obtained with immune checkpoint inhibitors, offer an ideal context and background to explore the major questions and future perspectives about the development of immunotherapeutic agents. In this regard, the choice of adequate endpoints, the use of modified statistical methods and the potential introduction of predictive biomarkers for immunotherapy clinical trials, will be discuss in this review in order to provide practical and rationale suggestions aimed to improve the existing model for cancer immunotherapy investigation.
authors.affiliation: 1 Department of Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy ; 2 Instituto Oncológico Dr Rosell, Quiron-Dexeus University Hospital, Barcelona, Spain ; 3 Istituto Nazionale Tumori, Milano, Italy ; 4 Italian Medicines Agency, Roma, Italy ; 5 Pangaea Biotech, Barcelona, Spain ; 6 Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain ; 7 Molecular Oncology Research (MORe) Foundation, Barcelona, Spain ; 8 Germans Trias i Pujol Health Sciences Institute and Hospital, Campus Can Ruti, Barcelona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Pilotto
authors.affiliation: 1 Department of Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy ; 2 Instituto Oncológico Dr Rosell, Quiron-Dexeus University Hospital, Barcelona, Spain ; 3 Istituto Nazionale Tumori, Milano, Italy ; 4 Italian Medicines Agency, Roma, Italy ; 5 Pangaea Biotech, Barcelona, Spain ; 6 Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain ; 7 Molecular Oncology Research (MORe) Foundation, Barcelona, Spain ; 8 Germans Trias i Pujol Health Sciences Institute and Hospital, Campus Can Ruti, Barcelona, Spain.
authors.forename: Luisa
authors.initials: L
authors.lastname: Carbognin
authors.affiliation: 1 Department of Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy ; 2 Instituto Oncológico Dr Rosell, Quiron-Dexeus University Hospital, Barcelona, Spain ; 3 Istituto Nazionale Tumori, Milano, Italy ; 4 Italian Medicines Agency, Roma, Italy ; 5 Pangaea Biotech, Barcelona, Spain ; 6 Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain ; 7 Molecular Oncology Research (MORe) Foundation, Barcelona, Spain ; 8 Germans Trias i Pujol Health Sciences Institute and Hospital, Campus Can Ruti, Barcelona, Spain.
authors.forename: Niki
authors.initials: N
authors.lastname: Karachaliou
authors.affiliation: 1 Department of Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy ; 2 Instituto Oncológico Dr Rosell, Quiron-Dexeus University Hospital, Barcelona, Spain ; 3 Istituto Nazionale Tumori, Milano, Italy ; 4 Italian Medicines Agency, Roma, Italy ; 5 Pangaea Biotech, Barcelona, Spain ; 6 Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain ; 7 Molecular Oncology Research (MORe) Foundation, Barcelona, Spain ; 8 Germans Trias i Pujol Health Sciences Institute and Hospital, Campus Can Ruti, Barcelona, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Garassino
authors.affiliation: 1 Department of Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy ; 2 Instituto Oncológico Dr Rosell, Quiron-Dexeus University Hospital, Barcelona, Spain ; 3 Istituto Nazionale Tumori, Milano, Italy ; 4 Italian Medicines Agency, Roma, Italy ; 5 Pangaea Biotech, Barcelona, Spain ; 6 Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain ; 7 Molecular Oncology Research (MORe) Foundation, Barcelona, Spain ; 8 Germans Trias i Pujol Health Sciences Institute and Hospital, Campus Can Ruti, Barcelona, Spain.
authors.forename: Federica
authors.initials: F
authors.lastname: Cuppone
authors.affiliation: 1 Department of Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy ; 2 Instituto Oncológico Dr Rosell, Quiron-Dexeus University Hospital, Barcelona, Spain ; 3 Istituto Nazionale Tumori, Milano, Italy ; 4 Italian Medicines Agency, Roma, Italy ; 5 Pangaea Biotech, Barcelona, Spain ; 6 Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain ; 7 Molecular Oncology Research (MORe) Foundation, Barcelona, Spain ; 8 Germans Trias i Pujol Health Sciences Institute and Hospital, Campus Can Ruti, Barcelona, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Petraglia
authors.affiliation: 1 Department of Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy ; 2 Instituto Oncológico Dr Rosell, Quiron-Dexeus University Hospital, Barcelona, Spain ; 3 Istituto Nazionale Tumori, Milano, Italy ; 4 Italian Medicines Agency, Roma, Italy ; 5 Pangaea Biotech, Barcelona, Spain ; 6 Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain ; 7 Molecular Oncology Research (MORe) Foundation, Barcelona, Spain ; 8 Germans Trias i Pujol Health Sciences Institute and Hospital, Campus Can Ruti, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
authors.affiliation: 1 Department of Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy ; 2 Instituto Oncológico Dr Rosell, Quiron-Dexeus University Hospital, Barcelona, Spain ; 3 Istituto Nazionale Tumori, Milano, Italy ; 4 Italian Medicines Agency, Roma, Italy ; 5 Pangaea Biotech, Barcelona, Spain ; 6 Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain ; 7 Molecular Oncology Research (MORe) Foundation, Barcelona, Spain ; 8 Germans Trias i Pujol Health Sciences Institute and Hospital, Campus Can Ruti, Barcelona, Spain.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Tortora
authors.affiliation: 1 Department of Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy ; 2 Instituto Oncológico Dr Rosell, Quiron-Dexeus University Hospital, Barcelona, Spain ; 3 Istituto Nazionale Tumori, Milano, Italy ; 4 Italian Medicines Agency, Roma, Italy ; 5 Pangaea Biotech, Barcelona, Spain ; 6 Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain ; 7 Molecular Oncology Research (MORe) Foundation, Barcelona, Spain ; 8 Germans Trias i Pujol Health Sciences Institute and Hospital, Campus Can Ruti, Barcelona, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Bria
keywords: Immunotherapy; cancer; design; lung; trial