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The New England journal of medicine
05 04, 2023;388 (18): 1657-1667.

Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer.

Gerald W Prager, Julien Taieb, Marwan Fakih, Fortunato Ciardiello, Eric Van Cutsem, Elena Elez, Felipe M Cruz, Lucjan Wyrwicz, Daniil Stroyakovskiy, Zsuzsanna P��pai, Pierre-Guillaume Poureau, Gabor Liposits, Chiara Cremolini, Igor Bondarenko, Dominik P Modest, Karim A Benhadji, Nadia Amellal, Catherine Leger, Lo��ck Vidot, Josep Tabernero, SUNLIGHT Investigators
Author Information
  1. Gerald W Prager: From the Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna (G.W.P.); the Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, SIRIC Cancer Research for Personalized Medicine, Universit�� Paris Cit��, Paris (J. Taieb), the Department of Oncology, University Hospital, Brest (P.-G.P.), and Servier, Suresnes (N.A., C.L., L.V.) - all in France; City of Hope Comprehensive Cancer Center, Duarte, CA (M.F.); Dipartimento di Medicina di Precisione, Universit�� degli Studi della Campania Luigi Vanvitelli, Naples (F.C.), and the Unit of Medical Oncology, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa (C.C.) - both in Italy; the Department of Digestive Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); the Department of Medical Oncology, Vall d'Hebron Hospital Campus and Institute of Oncology, International Oncology Bureau-Quiron, Barcelona (E.E., J. Tabernero); N��cleo de Pesquisa e Ensino da Rede S��o Camilo, S��o Paulo (F.M.C.); the Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (L.W.); Moscow City Oncology Hospital, Moscow Healthcare Department, Moscow (D.S.); the Department of Oncology, Hungarian Defense Forces Medical Center, Budapest, Hungary (Z.P.); the Department of Oncology, Regional Hospital West Jutland, Herning, Denmark (G.L.); Dnipro State Medical University, Dnipro, Ukraine (I.B.); the Medical Department of Hematology, Oncology, and Cancer Immunology, Charit��-Universit��tsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).
  2. Julien Taieb: From the Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna (G.W.P.); the Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, SIRIC Cancer Research for Personalized Medicine, Universit�� Paris Cit��, Paris (J. Taieb), the Department of Oncology, University Hospital, Brest (P.-G.P.), and Servier, Suresnes (N.A., C.L., L.V.) - all in France; City of Hope Comprehensive Cancer Center, Duarte, CA (M.F.); Dipartimento di Medicina di Precisione, Universit�� degli Studi della Campania Luigi Vanvitelli, Naples (F.C.), and the Unit of Medical Oncology, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa (C.C.) - both in Italy; the Department of Digestive Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); the Department of Medical Oncology, Vall d'Hebron Hospital Campus and Institute of Oncology, International Oncology Bureau-Quiron, Barcelona (E.E., J. Tabernero); N��cleo de Pesquisa e Ensino da Rede S��o Camilo, S��o Paulo (F.M.C.); the Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (L.W.); Moscow City Oncology Hospital, Moscow Healthcare Department, Moscow (D.S.); the Department of Oncology, Hungarian Defense Forces Medical Center, Budapest, Hungary (Z.P.); the Department of Oncology, Regional Hospital West Jutland, Herning, Denmark (G.L.); Dnipro State Medical University, Dnipro, Ukraine (I.B.); the Medical Department of Hematology, Oncology, and Cancer Immunology, Charit��-Universit��tsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).
  3. Marwan Fakih: From the Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna (G.W.P.); the Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, SIRIC Cancer Research for Personalized Medicine, Universit�� Paris Cit��, Paris (J. Taieb), the Department of Oncology, University Hospital, Brest (P.-G.P.), and Servier, Suresnes (N.A., C.L., L.V.) - all in France; City of Hope Comprehensive Cancer Center, Duarte, CA (M.F.); Dipartimento di Medicina di Precisione, Universit�� degli Studi della Campania Luigi Vanvitelli, Naples (F.C.), and the Unit of Medical Oncology, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa (C.C.) - both in Italy; the Department of Digestive Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); the Department of Medical Oncology, Vall d'Hebron Hospital Campus and Institute of Oncology, International Oncology Bureau-Quiron, Barcelona (E.E., J. Tabernero); N��cleo de Pesquisa e Ensino da Rede S��o Camilo, S��o Paulo (F.M.C.); the Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (L.W.); Moscow City Oncology Hospital, Moscow Healthcare Department, Moscow (D.S.); the Department of Oncology, Hungarian Defense Forces Medical Center, Budapest, Hungary (Z.P.); the Department of Oncology, Regional Hospital West Jutland, Herning, Denmark (G.L.); Dnipro State Medical University, Dnipro, Ukraine (I.B.); the Medical Department of Hematology, Oncology, and Cancer Immunology, Charit��-Universit��tsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).
  4. Fortunato Ciardiello: From the Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna (G.W.P.); the Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, SIRIC Cancer Research for Personalized Medicine, Universit�� Paris Cit��, Paris (J. Taieb), the Department of Oncology, University Hospital, Brest (P.-G.P.), and Servier, Suresnes (N.A., C.L., L.V.) - all in France; City of Hope Comprehensive Cancer Center, Duarte, CA (M.F.); Dipartimento di Medicina di Precisione, Universit�� degli Studi della Campania Luigi Vanvitelli, Naples (F.C.), and the Unit of Medical Oncology, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa (C.C.) - both in Italy; the Department of Digestive Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); the Department of Medical Oncology, Vall d'Hebron Hospital Campus and Institute of Oncology, International Oncology Bureau-Quiron, Barcelona (E.E., J. Tabernero); N��cleo de Pesquisa e Ensino da Rede S��o Camilo, S��o Paulo (F.M.C.); the Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (L.W.); Moscow City Oncology Hospital, Moscow Healthcare Department, Moscow (D.S.); the Department of Oncology, Hungarian Defense Forces Medical Center, Budapest, Hungary (Z.P.); the Department of Oncology, Regional Hospital West Jutland, Herning, Denmark (G.L.); Dnipro State Medical University, Dnipro, Ukraine (I.B.); the Medical Department of Hematology, Oncology, and Cancer Immunology, Charit��-Universit��tsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).
  5. Eric Van Cutsem: From the Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna (G.W.P.); the Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, SIRIC Cancer Research for Personalized Medicine, Universit�� Paris Cit��, Paris (J. Taieb), the Department of Oncology, University Hospital, Brest (P.-G.P.), and Servier, Suresnes (N.A., C.L., L.V.) - all in France; City of Hope Comprehensive Cancer Center, Duarte, CA (M.F.); Dipartimento di Medicina di Precisione, Universit�� degli Studi della Campania Luigi Vanvitelli, Naples (F.C.), and the Unit of Medical Oncology, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa (C.C.) - both in Italy; the Department of Digestive Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); the Department of Medical Oncology, Vall d'Hebron Hospital Campus and Institute of Oncology, International Oncology Bureau-Quiron, Barcelona (E.E., J. Tabernero); N��cleo de Pesquisa e Ensino da Rede S��o Camilo, S��o Paulo (F.M.C.); the Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (L.W.); Moscow City Oncology Hospital, Moscow Healthcare Department, Moscow (D.S.); the Department of Oncology, Hungarian Defense Forces Medical Center, Budapest, Hungary (Z.P.); the Department of Oncology, Regional Hospital West Jutland, Herning, Denmark (G.L.); Dnipro State Medical University, Dnipro, Ukraine (I.B.); the Medical Department of Hematology, Oncology, and Cancer Immunology, Charit��-Universit��tsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).
  6. Elena Elez: From the Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna (G.W.P.); the Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, SIRIC Cancer Research for Personalized Medicine, Universit�� Paris Cit��, Paris (J. Taieb), the Department of Oncology, University Hospital, Brest (P.-G.P.), and Servier, Suresnes (N.A., C.L., L.V.) - all in France; City of Hope Comprehensive Cancer Center, Duarte, CA (M.F.); Dipartimento di Medicina di Precisione, Universit�� degli Studi della Campania Luigi Vanvitelli, Naples (F.C.), and the Unit of Medical Oncology, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa (C.C.) - both in Italy; the Department of Digestive Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); the Department of Medical Oncology, Vall d'Hebron Hospital Campus and Institute of Oncology, International Oncology Bureau-Quiron, Barcelona (E.E., J. Tabernero); N��cleo de Pesquisa e Ensino da Rede S��o Camilo, S��o Paulo (F.M.C.); the Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (L.W.); Moscow City Oncology Hospital, Moscow Healthcare Department, Moscow (D.S.); the Department of Oncology, Hungarian Defense Forces Medical Center, Budapest, Hungary (Z.P.); the Department of Oncology, Regional Hospital West Jutland, Herning, Denmark (G.L.); Dnipro State Medical University, Dnipro, Ukraine (I.B.); the Medical Department of Hematology, Oncology, and Cancer Immunology, Charit��-Universit��tsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).
  7. Felipe M Cruz: From the Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna (G.W.P.); the Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, SIRIC Cancer Research for Personalized Medicine, Universit�� Paris Cit��, Paris (J. Taieb), the Department of Oncology, University Hospital, Brest (P.-G.P.), and Servier, Suresnes (N.A., C.L., L.V.) - all in France; City of Hope Comprehensive Cancer Center, Duarte, CA (M.F.); Dipartimento di Medicina di Precisione, Universit�� degli Studi della Campania Luigi Vanvitelli, Naples (F.C.), and the Unit of Medical Oncology, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa (C.C.) - both in Italy; the Department of Digestive Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); the Department of Medical Oncology, Vall d'Hebron Hospital Campus and Institute of Oncology, International Oncology Bureau-Quiron, Barcelona (E.E., J. Tabernero); N��cleo de Pesquisa e Ensino da Rede S��o Camilo, S��o Paulo (F.M.C.); the Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (L.W.); Moscow City Oncology Hospital, Moscow Healthcare Department, Moscow (D.S.); the Department of Oncology, Hungarian Defense Forces Medical Center, Budapest, Hungary (Z.P.); the Department of Oncology, Regional Hospital West Jutland, Herning, Denmark (G.L.); Dnipro State Medical University, Dnipro, Ukraine (I.B.); the Medical Department of Hematology, Oncology, and Cancer Immunology, Charit��-Universit��tsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).
  8. Lucjan Wyrwicz: From the Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna (G.W.P.); the Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, SIRIC Cancer Research for Personalized Medicine, Universit�� Paris Cit��, Paris (J. Taieb), the Department of Oncology, University Hospital, Brest (P.-G.P.), and Servier, Suresnes (N.A., C.L., L.V.) - all in France; City of Hope Comprehensive Cancer Center, Duarte, CA (M.F.); Dipartimento di Medicina di Precisione, Universit�� degli Studi della Campania Luigi Vanvitelli, Naples (F.C.), and the Unit of Medical Oncology, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa (C.C.) - both in Italy; the Department of Digestive Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); the Department of Medical Oncology, Vall d'Hebron Hospital Campus and Institute of Oncology, International Oncology Bureau-Quiron, Barcelona (E.E., J. Tabernero); N��cleo de Pesquisa e Ensino da Rede S��o Camilo, S��o Paulo (F.M.C.); the Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (L.W.); Moscow City Oncology Hospital, Moscow Healthcare Department, Moscow (D.S.); the Department of Oncology, Hungarian Defense Forces Medical Center, Budapest, Hungary (Z.P.); the Department of Oncology, Regional Hospital West Jutland, Herning, Denmark (G.L.); Dnipro State Medical University, Dnipro, Ukraine (I.B.); the Medical Department of Hematology, Oncology, and Cancer Immunology, Charit��-Universit��tsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).
  9. Daniil Stroyakovskiy: From the Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna (G.W.P.); the Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, SIRIC Cancer Research for Personalized Medicine, Universit�� Paris Cit��, Paris (J. Taieb), the Department of Oncology, University Hospital, Brest (P.-G.P.), and Servier, Suresnes (N.A., C.L., L.V.) - all in France; City of Hope Comprehensive Cancer Center, Duarte, CA (M.F.); Dipartimento di Medicina di Precisione, Universit�� degli Studi della Campania Luigi Vanvitelli, Naples (F.C.), and the Unit of Medical Oncology, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa (C.C.) - both in Italy; the Department of Digestive Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); the Department of Medical Oncology, Vall d'Hebron Hospital Campus and Institute of Oncology, International Oncology Bureau-Quiron, Barcelona (E.E., J. Tabernero); N��cleo de Pesquisa e Ensino da Rede S��o Camilo, S��o Paulo (F.M.C.); the Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (L.W.); Moscow City Oncology Hospital, Moscow Healthcare Department, Moscow (D.S.); the Department of Oncology, Hungarian Defense Forces Medical Center, Budapest, Hungary (Z.P.); the Department of Oncology, Regional Hospital West Jutland, Herning, Denmark (G.L.); Dnipro State Medical University, Dnipro, Ukraine (I.B.); the Medical Department of Hematology, Oncology, and Cancer Immunology, Charit��-Universit��tsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).
  10. Zsuzsanna P��pai: From the Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna (G.W.P.); the Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, SIRIC Cancer Research for Personalized Medicine, Universit�� Paris Cit��, Paris (J. Taieb), the Department of Oncology, University Hospital, Brest (P.-G.P.), and Servier, Suresnes (N.A., C.L., L.V.) - all in France; City of Hope Comprehensive Cancer Center, Duarte, CA (M.F.); Dipartimento di Medicina di Precisione, Universit�� degli Studi della Campania Luigi Vanvitelli, Naples (F.C.), and the Unit of Medical Oncology, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa (C.C.) - both in Italy; the Department of Digestive Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); the Department of Medical Oncology, Vall d'Hebron Hospital Campus and Institute of Oncology, International Oncology Bureau-Quiron, Barcelona (E.E., J. Tabernero); N��cleo de Pesquisa e Ensino da Rede S��o Camilo, S��o Paulo (F.M.C.); the Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (L.W.); Moscow City Oncology Hospital, Moscow Healthcare Department, Moscow (D.S.); the Department of Oncology, Hungarian Defense Forces Medical Center, Budapest, Hungary (Z.P.); the Department of Oncology, Regional Hospital West Jutland, Herning, Denmark (G.L.); Dnipro State Medical University, Dnipro, Ukraine (I.B.); the Medical Department of Hematology, Oncology, and Cancer Immunology, Charit��-Universit��tsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).
  11. Pierre-Guillaume Poureau: From the Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna (G.W.P.); the Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, SIRIC Cancer Research for Personalized Medicine, Universit�� Paris Cit��, Paris (J. Taieb), the Department of Oncology, University Hospital, Brest (P.-G.P.), and Servier, Suresnes (N.A., C.L., L.V.) - all in France; City of Hope Comprehensive Cancer Center, Duarte, CA (M.F.); Dipartimento di Medicina di Precisione, Universit�� degli Studi della Campania Luigi Vanvitelli, Naples (F.C.), and the Unit of Medical Oncology, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa (C.C.) - both in Italy; the Department of Digestive Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); the Department of Medical Oncology, Vall d'Hebron Hospital Campus and Institute of Oncology, International Oncology Bureau-Quiron, Barcelona (E.E., J. Tabernero); N��cleo de Pesquisa e Ensino da Rede S��o Camilo, S��o Paulo (F.M.C.); the Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (L.W.); Moscow City Oncology Hospital, Moscow Healthcare Department, Moscow (D.S.); the Department of Oncology, Hungarian Defense Forces Medical Center, Budapest, Hungary (Z.P.); the Department of Oncology, Regional Hospital West Jutland, Herning, Denmark (G.L.); Dnipro State Medical University, Dnipro, Ukraine (I.B.); the Medical Department of Hematology, Oncology, and Cancer Immunology, Charit��-Universit��tsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).
  12. Gabor Liposits: From the Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna (G.W.P.); the Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, SIRIC Cancer Research for Personalized Medicine, Universit�� Paris Cit��, Paris (J. Taieb), the Department of Oncology, University Hospital, Brest (P.-G.P.), and Servier, Suresnes (N.A., C.L., L.V.) - all in France; City of Hope Comprehensive Cancer Center, Duarte, CA (M.F.); Dipartimento di Medicina di Precisione, Universit�� degli Studi della Campania Luigi Vanvitelli, Naples (F.C.), and the Unit of Medical Oncology, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa (C.C.) - both in Italy; the Department of Digestive Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); the Department of Medical Oncology, Vall d'Hebron Hospital Campus and Institute of Oncology, International Oncology Bureau-Quiron, Barcelona (E.E., J. Tabernero); N��cleo de Pesquisa e Ensino da Rede S��o Camilo, S��o Paulo (F.M.C.); the Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (L.W.); Moscow City Oncology Hospital, Moscow Healthcare Department, Moscow (D.S.); the Department of Oncology, Hungarian Defense Forces Medical Center, Budapest, Hungary (Z.P.); the Department of Oncology, Regional Hospital West Jutland, Herning, Denmark (G.L.); Dnipro State Medical University, Dnipro, Ukraine (I.B.); the Medical Department of Hematology, Oncology, and Cancer Immunology, Charit��-Universit��tsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).
  13. Chiara Cremolini: From the Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna (G.W.P.); the Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, SIRIC Cancer Research for Personalized Medicine, Universit�� Paris Cit��, Paris (J. Taieb), the Department of Oncology, University Hospital, Brest (P.-G.P.), and Servier, Suresnes (N.A., C.L., L.V.) - all in France; City of Hope Comprehensive Cancer Center, Duarte, CA (M.F.); Dipartimento di Medicina di Precisione, Universit�� degli Studi della Campania Luigi Vanvitelli, Naples (F.C.), and the Unit of Medical Oncology, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa (C.C.) - both in Italy; the Department of Digestive Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); the Department of Medical Oncology, Vall d'Hebron Hospital Campus and Institute of Oncology, International Oncology Bureau-Quiron, Barcelona (E.E., J. Tabernero); N��cleo de Pesquisa e Ensino da Rede S��o Camilo, S��o Paulo (F.M.C.); the Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (L.W.); Moscow City Oncology Hospital, Moscow Healthcare Department, Moscow (D.S.); the Department of Oncology, Hungarian Defense Forces Medical Center, Budapest, Hungary (Z.P.); the Department of Oncology, Regional Hospital West Jutland, Herning, Denmark (G.L.); Dnipro State Medical University, Dnipro, Ukraine (I.B.); the Medical Department of Hematology, Oncology, and Cancer Immunology, Charit��-Universit��tsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).
  14. Igor Bondarenko: From the Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna (G.W.P.); the Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, SIRIC Cancer Research for Personalized Medicine, Universit�� Paris Cit��, Paris (J. Taieb), the Department of Oncology, University Hospital, Brest (P.-G.P.), and Servier, Suresnes (N.A., C.L., L.V.) - all in France; City of Hope Comprehensive Cancer Center, Duarte, CA (M.F.); Dipartimento di Medicina di Precisione, Universit�� degli Studi della Campania Luigi Vanvitelli, Naples (F.C.), and the Unit of Medical Oncology, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa (C.C.) - both in Italy; the Department of Digestive Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); the Department of Medical Oncology, Vall d'Hebron Hospital Campus and Institute of Oncology, International Oncology Bureau-Quiron, Barcelona (E.E., J. Tabernero); N��cleo de Pesquisa e Ensino da Rede S��o Camilo, S��o Paulo (F.M.C.); the Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (L.W.); Moscow City Oncology Hospital, Moscow Healthcare Department, Moscow (D.S.); the Department of Oncology, Hungarian Defense Forces Medical Center, Budapest, Hungary (Z.P.); the Department of Oncology, Regional Hospital West Jutland, Herning, Denmark (G.L.); Dnipro State Medical University, Dnipro, Ukraine (I.B.); the Medical Department of Hematology, Oncology, and Cancer Immunology, Charit��-Universit��tsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).
  15. Dominik P Modest: From the Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna (G.W.P.); the Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, SIRIC Cancer Research for Personalized Medicine, Universit�� Paris Cit��, Paris (J. Taieb), the Department of Oncology, University Hospital, Brest (P.-G.P.), and Servier, Suresnes (N.A., C.L., L.V.) - all in France; City of Hope Comprehensive Cancer Center, Duarte, CA (M.F.); Dipartimento di Medicina di Precisione, Universit�� degli Studi della Campania Luigi Vanvitelli, Naples (F.C.), and the Unit of Medical Oncology, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa (C.C.) - both in Italy; the Department of Digestive Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); the Department of Medical Oncology, Vall d'Hebron Hospital Campus and Institute of Oncology, International Oncology Bureau-Quiron, Barcelona (E.E., J. Tabernero); N��cleo de Pesquisa e Ensino da Rede S��o Camilo, S��o Paulo (F.M.C.); the Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (L.W.); Moscow City Oncology Hospital, Moscow Healthcare Department, Moscow (D.S.); the Department of Oncology, Hungarian Defense Forces Medical Center, Budapest, Hungary (Z.P.); the Department of Oncology, Regional Hospital West Jutland, Herning, Denmark (G.L.); Dnipro State Medical University, Dnipro, Ukraine (I.B.); the Medical Department of Hematology, Oncology, and Cancer Immunology, Charit��-Universit��tsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).
  16. Karim A Benhadji: From the Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna (G.W.P.); the Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, SIRIC Cancer Research for Personalized Medicine, Universit�� Paris Cit��, Paris (J. Taieb), the Department of Oncology, University Hospital, Brest (P.-G.P.), and Servier, Suresnes (N.A., C.L., L.V.) - all in France; City of Hope Comprehensive Cancer Center, Duarte, CA (M.F.); Dipartimento di Medicina di Precisione, Universit�� degli Studi della Campania Luigi Vanvitelli, Naples (F.C.), and the Unit of Medical Oncology, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa (C.C.) - both in Italy; the Department of Digestive Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); the Department of Medical Oncology, Vall d'Hebron Hospital Campus and Institute of Oncology, International Oncology Bureau-Quiron, Barcelona (E.E., J. Tabernero); N��cleo de Pesquisa e Ensino da Rede S��o Camilo, S��o Paulo (F.M.C.); the Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (L.W.); Moscow City Oncology Hospital, Moscow Healthcare Department, Moscow (D.S.); the Department of Oncology, Hungarian Defense Forces Medical Center, Budapest, Hungary (Z.P.); the Department of Oncology, Regional Hospital West Jutland, Herning, Denmark (G.L.); Dnipro State Medical University, Dnipro, Ukraine (I.B.); the Medical Department of Hematology, Oncology, and Cancer Immunology, Charit��-Universit��tsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.). ORCID
  17. Nadia Amellal: From the Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna (G.W.P.); the Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, SIRIC Cancer Research for Personalized Medicine, Universit�� Paris Cit��, Paris (J. Taieb), the Department of Oncology, University Hospital, Brest (P.-G.P.), and Servier, Suresnes (N.A., C.L., L.V.) - all in France; City of Hope Comprehensive Cancer Center, Duarte, CA (M.F.); Dipartimento di Medicina di Precisione, Universit�� degli Studi della Campania Luigi Vanvitelli, Naples (F.C.), and the Unit of Medical Oncology, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa (C.C.) - both in Italy; the Department of Digestive Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); the Department of Medical Oncology, Vall d'Hebron Hospital Campus and Institute of Oncology, International Oncology Bureau-Quiron, Barcelona (E.E., J. Tabernero); N��cleo de Pesquisa e Ensino da Rede S��o Camilo, S��o Paulo (F.M.C.); the Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (L.W.); Moscow City Oncology Hospital, Moscow Healthcare Department, Moscow (D.S.); the Department of Oncology, Hungarian Defense Forces Medical Center, Budapest, Hungary (Z.P.); the Department of Oncology, Regional Hospital West Jutland, Herning, Denmark (G.L.); Dnipro State Medical University, Dnipro, Ukraine (I.B.); the Medical Department of Hematology, Oncology, and Cancer Immunology, Charit��-Universit��tsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).
  18. Catherine Leger: From the Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna (G.W.P.); the Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, SIRIC Cancer Research for Personalized Medicine, Universit�� Paris Cit��, Paris (J. Taieb), the Department of Oncology, University Hospital, Brest (P.-G.P.), and Servier, Suresnes (N.A., C.L., L.V.) - all in France; City of Hope Comprehensive Cancer Center, Duarte, CA (M.F.); Dipartimento di Medicina di Precisione, Universit�� degli Studi della Campania Luigi Vanvitelli, Naples (F.C.), and the Unit of Medical Oncology, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa (C.C.) - both in Italy; the Department of Digestive Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); the Department of Medical Oncology, Vall d'Hebron Hospital Campus and Institute of Oncology, International Oncology Bureau-Quiron, Barcelona (E.E., J. Tabernero); N��cleo de Pesquisa e Ensino da Rede S��o Camilo, S��o Paulo (F.M.C.); the Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (L.W.); Moscow City Oncology Hospital, Moscow Healthcare Department, Moscow (D.S.); the Department of Oncology, Hungarian Defense Forces Medical Center, Budapest, Hungary (Z.P.); the Department of Oncology, Regional Hospital West Jutland, Herning, Denmark (G.L.); Dnipro State Medical University, Dnipro, Ukraine (I.B.); the Medical Department of Hematology, Oncology, and Cancer Immunology, Charit��-Universit��tsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).
  19. Lo��ck Vidot: From the Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna (G.W.P.); the Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, SIRIC Cancer Research for Personalized Medicine, Universit�� Paris Cit��, Paris (J. Taieb), the Department of Oncology, University Hospital, Brest (P.-G.P.), and Servier, Suresnes (N.A., C.L., L.V.) - all in France; City of Hope Comprehensive Cancer Center, Duarte, CA (M.F.); Dipartimento di Medicina di Precisione, Universit�� degli Studi della Campania Luigi Vanvitelli, Naples (F.C.), and the Unit of Medical Oncology, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa (C.C.) - both in Italy; the Department of Digestive Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); the Department of Medical Oncology, Vall d'Hebron Hospital Campus and Institute of Oncology, International Oncology Bureau-Quiron, Barcelona (E.E., J. Tabernero); N��cleo de Pesquisa e Ensino da Rede S��o Camilo, S��o Paulo (F.M.C.); the Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (L.W.); Moscow City Oncology Hospital, Moscow Healthcare Department, Moscow (D.S.); the Department of Oncology, Hungarian Defense Forces Medical Center, Budapest, Hungary (Z.P.); the Department of Oncology, Regional Hospital West Jutland, Herning, Denmark (G.L.); Dnipro State Medical University, Dnipro, Ukraine (I.B.); the Medical Department of Hematology, Oncology, and Cancer Immunology, Charit��-Universit��tsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).
  20. Josep Tabernero: From the Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna (G.W.P.); the Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, SIRIC Cancer Research for Personalized Medicine, Universit�� Paris Cit��, Paris (J. Taieb), the Department of Oncology, University Hospital, Brest (P.-G.P.), and Servier, Suresnes (N.A., C.L., L.V.) - all in France; City of Hope Comprehensive Cancer Center, Duarte, CA (M.F.); Dipartimento di Medicina di Precisione, Universit�� degli Studi della Campania Luigi Vanvitelli, Naples (F.C.), and the Unit of Medical Oncology, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa (C.C.) - both in Italy; the Department of Digestive Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium (E.V.C.); the Department of Medical Oncology, Vall d'Hebron Hospital Campus and Institute of Oncology, International Oncology Bureau-Quiron, Barcelona (E.E., J. Tabernero); N��cleo de Pesquisa e Ensino da Rede S��o Camilo, S��o Paulo (F.M.C.); the Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (L.W.); Moscow City Oncology Hospital, Moscow Healthcare Department, Moscow (D.S.); the Department of Oncology, Hungarian Defense Forces Medical Center, Budapest, Hungary (Z.P.); the Department of Oncology, Regional Hospital West Jutland, Herning, Denmark (G.L.); Dnipro State Medical University, Dnipro, Ukraine (I.B.); the Medical Department of Hematology, Oncology, and Cancer Immunology, Charit��-Universit��tsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).
PMID: 37133585 DOI: 10.1056/NEJMoa2214963

Abstract

BACKGROUND: In a previous phase 3 trial, treatment with trifluridine-tipiracil (FTD-TPI) prolonged overall survival among patients with metastatic colorectal cancer. Preliminary data from single-group and randomized phase 2 trials suggest that treatment with FTD-TPI in addition to bevacizumab has the potential to extend survival.
METHODS: We randomly assigned, in a 1:1 ratio, adult patients who had received no more than two previous chemotherapy regimens for the treatment of advanced colorectal cancer to receive FTD-TPI plus bevacizumab (combination group) or FTD-TPI alone (FTD-TPI group). The primary end point was overall survival. Secondary end points were progression-free survival and safety, including the time to worsening of the Eastern Cooperative Oncology Group (ECOG) performance-status score from 0 or 1 to 2 or more (on a scale from 0 to 5, with higher scores indicating greater disability).
RESULTS: A total of 246 patients were assigned to each group. The median overall survival was 10.8 months in the combination group and 7.5 months in the FTD-TPI group (hazard ratio for death, 0.61; 95% confidence interval [CI], 0.49 to 0.77; P<0.001). The median progression-free survival was 5.6 months in the combination group and 2.4 months in the FTD-TPI group (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.54; P<0.001). The most common adverse events in both groups were neutropenia, nausea, and anemia. No treatment-related deaths were reported. The median time to worsening of the ECOG performance-status score from 0 or 1 to 2 or more was 9.3 months in the combination group and 6.3 months in the FTD-TPI group (hazard ratio, 0.54; 95% CI, 0.43 to 0.67).
CONCLUSIONS: Among patients with refractory metastatic colorectal cancer, treatment with FTD-TPI plus bevacizumab resulted in longer overall survival than FTD-TPI alone. (Funded by Servier and Taiho Oncology; SUNLIGHT ClinicalTrials.gov number, NCT04737187; EudraCT number, 2020-001976-14.).

Associated Data

ClinicalTrials.gov | NCT04737187
EudraCT | 2020-001976-14

Grants

  1. N/A/Servier

MeSH Term

Adult
Humans
Antineoplastic Combined Chemotherapy Protocols
Bevacizumab
Colonic Neoplasms
Colorectal Neoplasms
Drug Combinations
Pyrrolidines
Rectal Neoplasms
Trifluridine
Uracil

Chemicals

Bevacizumab
Drug Combinations
Pyrrolidines
tipiracil
Trifluridine
Uracil
Journal Article Randomized Controlled Trial
Article has an altmetric score of 1140

Word Cloud

Created with Highcharts 10.0.00FTD-TPIgroupsurvivalmonthstreatmentoverallpatients2ratiocombination3colorectalcancerbevacizumab5medianhazard95%previousphasemetastaticassignedplusaloneendprogression-freetimeworseningOncologyECOGperformance-statusscore1deathP<00016CI54numberBACKGROUND:trialtrifluridine-tipiracilprolongedamongPreliminarydatasingle-grouprandomizedtrialssuggestadditionpotentialextendMETHODS:randomly1:1adultreceivedtwochemotherapyregimensadvancedreceiveprimarypointSecondarypointssafetyincludingEasternCooperativeGroupscalehigherscoresindicatinggreaterdisabilityRESULTS:total246108761confidenceinterval[CI]49774diseaseprogression4436commonadverseeventsgroupsneutropenianauseaanemiatreatment-relateddeathsreported94367CONCLUSIONS:AmongrefractoryresultedlongerFundedServierTaihoSUNLIGHTClinicalTrialsgovNCT04737187EudraCT2020-001976-14Trifluridine-TipiracilBevacizumabRefractoryMetastaticColorectalCancer

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