Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer.


Journal

The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562

Informations de publication

Date de publication:
04 May 2023
Historique:
medline: 5 5 2023
pubmed: 3 5 2023
entrez: 3 5 2023
Statut: ppublish

Résumé

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. 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). 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). 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.).

Sections du résumé

BACKGROUND 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 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 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 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.).

Identifiants

pubmed: 37133585
doi: 10.1056/NEJMoa2214963
doi:

Substances chimiques

Bevacizumab 2S9ZZM9Q9V
Drug Combinations 0
Pyrrolidines 0
tipiracil NGO10K751P
Trifluridine RMW9V5RW38
Uracil 56HH86ZVCT

Banques de données

ClinicalTrials.gov
['NCT04737187']
EudraCT
['2020-001976-14']

Types de publication

Journal Article Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

1657-1667

Subventions

Organisme : Servier
ID : N/A

Investigateurs

Arno Amann (A)
Armin Gerger (A)
Richard Greil (R)
Birgit Gruenberger (B)
Ulrich Popper (U)
Gerald Prager (G)
Thomas Winder (T)
Koen Hendrickx (K)
Ghislain Houbiers (G)
Willem Lybaert (W)
Marc Peeters (M)
Eric Van Custem (E)
Káthia Cristina Abdalla (KC)
Arinilda Campos Bragagnoli (A)
Roberto Carmagani Pestana (R)
Felipe José Silva Melo Cruz (FJSM)
Mauro Daniel Spina Donadio (MD)
Gustavo Dos Santos Fernandes (GDS)
Camila Motta Venchiarutti Moniz (CMV)
Gabor Istvan Liposits (GI)
Rene Olesen (R)
Lone Nørgård Petersen (LN)
Per Pfeiffer (P)
Christophe Borg (C)
Helene Boussion (H)
Marie-Pierre Galais (MP)
Pierre-Guillaume Poureau (PG)
Julien Taieb (J)
David Tougeron (D)
Volker Heinemann (V)
Jens Kisro (J)
Dominik Paul Modest (DP)
Ingo Schwaner (I)
Péter Arkosy (P)
György Bodoky (G)
András Csejtei (A)
Tibor Csöszi (T)
Zsolt Horvath (Z)
Zoltan Nagy (Z)
Judith Olah (J)
Zsuzsanna Pápai (Z)
István Sipöcz (I)
Antonio Avallone (A)
Maria Banzi (M)
Domenico Bilancia (D)
Fortunato Ciardiello (F)
Chiara Cremolini (C)
Sara Lonardi (S)
Evaristo Maiello (E)
Nicola Personeni (N)
Mario Scartozzi (M)
Renata Duchnowska (R)
Bartosz Itrych (B)
Bogusława Karaszewska (B)
Barbara Radecka (B)
Wojciech Rogowski (W)
Lucjan Wyrwicz (L)
Piotr Wysocki (P)
Mikhail Fedyanin (M)
Dmitry Kirtbaya (D)
Nikolay Kislov (N)
Mikhail Kopp (M)
Ludmila Lebedeva (L)
Evgeny Ledin (E)
Yulia Makarova (Y)
Fedor Moiseenko (F)
Rashida Orlova (R)
Irina Radyukova (I)
Tatiana Semiglazova (T)
Daniil Stroyakovskyi (D)
Sergei A Tjulandin (SA)
Elena Élez (E)
Reyes Ferreiro-Monteagudo (R)
Cristina Grávalos-Castro (C)
Eduardo Polo-Marqués (E)
Vanessa Pachón Olmos (V)
María José Ortiz-Morales (MJ)
Fernando Rivera (F)
María José Safont (MJ)
Gemma Soler (G)
Josep Tabernero (J)
Manuel Valladares Ayerbes (M)
Anna C Virgili Manrique (AC)
Igor Bondarekno (I)
Iryna Kolachko (I)
Stepan Krulko (S)
Yuriy Ostapenko (Y)
Viktor Paramonov (V)
Olga Ponomarova (O)
Dinara Ryspayeva (D)
Serhii Shevnia (S)
Yaroslav Shparyk (Y)
Tanios S Bekaii-Saab (TS)
Ruemu E Birhiray (RE)
Nafisa Burhani (N)
Marcia Cruz-Correa (M)
Mike Cusnir (M)
Pratibha Desai (P)
Marwan G Fakih (MG)
Ryan Hall (R)
Zhaohui Jin (Z)
Jeremy C Jones (JC)
Jonathan Lu (J)
Nagendra Natarajan (N)
Haroutioun Shahinian (H)

Commentaires et corrections

Type : CommentIn
Type : CommentIn
Type : CommentIn

Informations de copyright

Copyright © 2023 Massachusetts Medical Society.

Auteurs

Gerald W Prager (GW)

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, Université Paris Cité, 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, Università 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); Núcleo de Pesquisa e Ensino da Rede São Camilo, São 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, Charité-Universitätsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).

Julien Taieb (J)

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, Université Paris Cité, 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, Università 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); Núcleo de Pesquisa e Ensino da Rede São Camilo, São 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, Charité-Universitätsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).

Marwan Fakih (M)

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, Université Paris Cité, 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, Università 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); Núcleo de Pesquisa e Ensino da Rede São Camilo, São 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, Charité-Universitätsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).

Fortunato Ciardiello (F)

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, Université Paris Cité, 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, Università 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); Núcleo de Pesquisa e Ensino da Rede São Camilo, São 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, Charité-Universitätsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).

Eric Van Cutsem (E)

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, Université Paris Cité, 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, Università 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); Núcleo de Pesquisa e Ensino da Rede São Camilo, São 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, Charité-Universitätsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).

Elena Elez (E)

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, Université Paris Cité, 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, Università 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); Núcleo de Pesquisa e Ensino da Rede São Camilo, São 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, Charité-Universitätsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).

Felipe M Cruz (FM)

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, Université Paris Cité, 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, Università 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); Núcleo de Pesquisa e Ensino da Rede São Camilo, São 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, Charité-Universitätsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).

Lucjan Wyrwicz (L)

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, Université Paris Cité, 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, Università 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); Núcleo de Pesquisa e Ensino da Rede São Camilo, São 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, Charité-Universitätsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).

Daniil Stroyakovskiy (D)

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, Université Paris Cité, 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, Università 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); Núcleo de Pesquisa e Ensino da Rede São Camilo, São 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, Charité-Universitätsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).

Zsuzsanna Pápai (Z)

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, Université Paris Cité, 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, Università 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); Núcleo de Pesquisa e Ensino da Rede São Camilo, São 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, Charité-Universitätsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).

Pierre-Guillaume Poureau (PG)

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, Université Paris Cité, 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, Università 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); Núcleo de Pesquisa e Ensino da Rede São Camilo, São 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, Charité-Universitätsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).

Gabor Liposits (G)

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, Université Paris Cité, 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, Università 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); Núcleo de Pesquisa e Ensino da Rede São Camilo, São 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, Charité-Universitätsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).

Chiara Cremolini (C)

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, Université Paris Cité, 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, Università 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); Núcleo de Pesquisa e Ensino da Rede São Camilo, São 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, Charité-Universitätsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).

Igor Bondarenko (I)

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, Université Paris Cité, 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, Università 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); Núcleo de Pesquisa e Ensino da Rede São Camilo, São 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, Charité-Universitätsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).

Dominik P Modest (DP)

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, Université Paris Cité, 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, Università 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); Núcleo de Pesquisa e Ensino da Rede São Camilo, São 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, Charité-Universitätsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).

Karim A Benhadji (KA)

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, Université Paris Cité, 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, Università 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); Núcleo de Pesquisa e Ensino da Rede São Camilo, São 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, Charité-Universitätsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).

Nadia Amellal (N)

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, Université Paris Cité, 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, Università 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); Núcleo de Pesquisa e Ensino da Rede São Camilo, São 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, Charité-Universitätsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).

Catherine Leger (C)

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, Université Paris Cité, 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, Università 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); Núcleo de Pesquisa e Ensino da Rede São Camilo, São 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, Charité-Universitätsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).

Loïck Vidot (L)

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, Université Paris Cité, 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, Università 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); Núcleo de Pesquisa e Ensino da Rede São Camilo, São 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, Charité-Universitätsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).

Josep Tabernero (J)

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, Université Paris Cité, 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, Università 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); Núcleo de Pesquisa e Ensino da Rede São Camilo, São 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, Charité-Universitätsmedizin Berlin, Berlin (D.P.M.); and Taiho Oncology, Princeton, NJ (K.A.B.).

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