Nivolumab plus Ipilimumab in Microsatellite-Instability-High Metastatic Colorectal Cancer.

Autor:	Andre T; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., Elez E; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., Van Cutsem E; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., Jensen LH; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., Bennouna J; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., Mendez G; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., Schenker M; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., de la Fouchardiere C; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., Limon ML; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., Yoshino T; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., Li J; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., Lenz HJ; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., Manzano Mozo JL; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., Tortora G; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., Garcia-Carbonero R; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., Dahan L; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., Chalabi M; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., Joshi R; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., Goekkurt E; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., Braghiroli MI; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., Cil T; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., Cela E; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., Chen T; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., Lei M; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., Dixon M; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., Abdullaev S; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.)., Lonardi S; From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.).
Jazyk:	angličtina
Zdroj:	The New England journal of medicine [N Engl J Med] 2024 Nov 28; Vol. 391 (21), pp. 2014-2026.
DOI:	10.1056/NEJMoa2402141
Abstrakt:	Background: Patients with microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) metastatic colorectal cancer have poor outcomes with standard chemotherapy with or without targeted therapies. Nivolumab plus ipilimumab has shown clinical benefit in nonrandomized studies of MSI-H or dMMR metastatic colorectal cancer. Methods: In this phase 3 open-label trial, we randomly assigned patients with unresectable or metastatic colorectal cancer and MSI-H or dMMR status according to local testing to receive, in a 2:2:1 ratio, nivolumab plus ipilimumab, nivolumab alone, or chemotherapy with or without targeted therapies. The dual primary end points, assessed in patients with centrally confirmed MSI-H or dMMR status, were progression-free survival with nivolumab plus ipilimumab as compared with chemotherapy as first-line therapy and progression-free survival with nivolumab plus ipilimumab as compared with nivolumab alone in patients regardless of previous systemic treatment for metastatic disease. At this prespecified interim analysis, the first primary end point (involving nivolumab plus ipilimumab vs. chemotherapy) was assessed. Results: A total of 303 patients who had not previously received systemic treatment for metastatic disease were randomly assigned to receive nivolumab plus ipilimumab or chemotherapy; 255 patients had centrally confirmed MSI-H or dMMR tumors. At a median follow-up of 31.5 months (range, 6.1 to 48.4), progression-free survival outcomes (the primary analysis) were significantly better with nivolumab plus ipilimumab than with chemotherapy (P<0.001 for the between-group difference in progression-free survival, calculated with the use of a two-sided stratified log-rank test); 24-month progression-free survival was 72% (95% confidence interval [CI], 64 to 79) with nivolumab plus ipilimumab as compared with 14% (95% CI, 6 to 25) with chemotherapy. At 24 months, the restricted mean survival time was 10.6 months (95% CI, 8.4 to 12.9) longer with nivolumab plus ipilimumab than with chemotherapy, a finding consistent with the primary analysis of progression-free survival. Grade 3 or 4 treatment-related adverse events occurred in 23% of the patients in the nivolumab-plus-ipilimumab group and in 48% of the patients in the chemotherapy group. Conclusions: Progression-free survival was longer with nivolumab plus ipilimumab than with chemotherapy among patients who had not previously received systemic treatment for MSI-H or dMMR metastatic colorectal cancer. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 8HW ClinicalTrials.gov number, NCT04008030.). (Copyright © 2024 Massachusetts Medical Society.)
Databáze:	MEDLINE
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