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أعرض في EDS

Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer.

التفاصيل البيبلوغرافية
العنوان: Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer.
المؤلفون: Kopetz S; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Grothey A; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Yaeger R; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Van Cutsem E; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Desai J; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Yoshino T; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Wasan H; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Ciardiello F; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Loupakis F; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Hong YS; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Steeghs N; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Guren TK; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Arkenau HT; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Garcia-Alfonso P; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Pfeiffer P; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Orlov S; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Lonardi S; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Elez E; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Kim TW; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Schellens JHM; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Guo C; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Krishnan A; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Dekervel J; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Morris V; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Calvo Ferrandiz A; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Tarpgaard LS; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Braun M; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Gollerkeri A; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Keir C; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Maharry K; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Pickard M; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Christy-Bittel J; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Anderson L; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Sandor V; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.)., Tabernero J; From the University of Texas M.D. Anderson Cancer Center, Houston (S.K., V.M.); West Cancer Center and Research Institute, OneOncology, Germantown, TN (A. Grothey); Memorial Sloan Kettering Cancer Center, New York (R.Y., A.K.); University Hospital Gasthuisberg and University of Leuven, Leuven, Belgium (E.V.C., J. Dekervel); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (J. Desai, C.G.); National Cancer Center Hospital East, Kashiwa, Japan (T.Y.); Hammersmith Hospital, Division of Cancer, Imperial College London (H.W.), and the Sarah Cannon Research Institute and University College London Cancer Institute (H.-T.A.), London, and the Christie NHS Foundation Trust/National Institute for Health Research Manchester Biomedical Research Centre, Manchester (M.B.) - all in the United Kingdom; the University of Campania Luigi Vanvitelli, Naples (F.C.), and Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padua (F.L., S.L.) - both in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (Y.S.H., T.-W.K.); the Netherlands Cancer Institute, Amsterdam (N.S., J.H.M.S.); Oslo University Hospital, Oslo (T.K.G.); Hospital Gregorio Marañón, Madrid (P.G.-A., A.C.F.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, UVic, IOB-Quiron, Barcelona (E.E., J.T.) - both in Spain; Odense University Hospital, Odense, Denmark (P.P., L.S.T.); Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia (S.O.); and Array BioPharma, Boulder, CO (A. Gollerkeri, C.K., K.M., M.P., J.C.-B., L.A., V.S.).
المصدر: The New England journal of medicine [N Engl J Med] 2019 Oct 24; Vol. 381 (17), pp. 1632-1643. Date of Electronic Publication: 2019 Sep 30.
نوع المنشور: Clinical Trial, Phase III; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Massachusetts Medical Society Country of Publication: United States NLM ID: 0255562 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1533-4406 (Electronic) Linking ISSN: 00284793 NLM ISO Abbreviation: N Engl J Med Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Boston, Massachusetts Medical Society.
مواضيع طبية MeSH: Mutation*, Antineoplastic Combined Chemotherapy Protocols/*therapeutic use , Benzimidazoles/*administration & dosage , Carbamates/*administration & dosage , Cetuximab/*administration & dosage , Colorectal Neoplasms/*drug therapy , Proto-Oncogene Proteins B-raf/*genetics , Sulfonamides/*administration & dosage, Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/mortality ; Disease Progression ; Electrocorticography ; Female ; Humans ; Intention to Treat Analysis ; Irinotecan/therapeutic use ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Survival Analysis
مستخلص: Background: Patients with metastatic colorectal cancer with the BRAF V600E mutation have a poor prognosis, with a median overall survival of 4 to 6 months after failure of initial therapy. Inhibition of BRAF alone has limited activity because of pathway reactivation through epidermal growth factor receptor signaling.
Methods: In this open-label, phase 3 trial, we enrolled 665 patients with BRAF V600E-mutated metastatic colorectal cancer who had had disease progression after one or two previous regimens. Patients were randomly assigned in a 1:1:1 ratio to receive encorafenib, binimetinib, and cetuximab (triplet-therapy group); encorafenib and cetuximab (doublet-therapy group); or the investigators' choice of either cetuximab and irinotecan or cetuximab and FOLFIRI (folinic acid, fluorouracil, and irinotecan) (control group). The primary end points were overall survival and objective response rate in the triplet-therapy group as compared with the control group. A secondary end point was overall survival in the doublet-therapy group as compared with the control group. We report here the results of a prespecified interim analysis.
Results: The median overall survival was 9.0 months in the triplet-therapy group and 5.4 months in the control group (hazard ratio for death, 0.52; 95% confidence interval [CI], 0.39 to 0.70; P<0.001). The confirmed response rate was 26% (95% CI, 18 to 35) in the triplet-therapy group and 2% (95% CI, 0 to 7) in the control group (P<0.001). The median overall survival in the doublet-therapy group was 8.4 months (hazard ratio for death vs. control, 0.60; 95% CI, 0.45 to 0.79; P<0.001). Adverse events of grade 3 or higher occurred in 58% of patients in the triplet-therapy group, in 50% in the doublet-therapy group, and in 61% in the control group.
Conclusions: A combination of encorafenib, cetuximab, and binimetinib resulted in significantly longer overall survival and a higher response rate than standard therapy in patients with metastatic colorectal cancer with the BRAF V600E mutation. (Funded by Array BioPharma and others; BEACON CRC ClinicalTrials.gov number, NCT02928224; EudraCT number, 2015-005805-35.).
(Copyright © 2019 Massachusetts Medical Society.)
التعليقات: Comment in: Nat Rev Clin Oncol. 2019 Dec;16(12):723. (PMID: 31601986)
Comment in: N Engl J Med. 2020 Feb 27;382(9):876. (PMID: 32101675)
Comment in: N Engl J Med. 2020 Feb 27;382(9):876. (PMID: 32101676)
Comment in: N Engl J Med. 2020 Feb 27;382(9):876-877. (PMID: 32101677)
سلسلة جزيئية: ClinicalTrials.gov NCT02928224
EudraCT 2015-005805-35
المشرفين على المادة: 0 (Benzimidazoles)
0 (Carbamates)
0 (Sulfonamides)
181R97MR71 (binimetinib)
7673326042 (Irinotecan)
8L7891MRB6 (encorafenib)
EC 2.7.11.1 (BRAF protein, human)
EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
PQX0D8J21J (Cetuximab)
تواريخ الأحداث: Date Created: 20191001 Date Completed: 20191106 Latest Revision: 20191210
رمز التحديث: 20231215
DOI: 10.1056/NEJMoa1908075
PMID: 31566309
قاعدة البيانات: MEDLINE
الوصف
تدمد:1533-4406
DOI:10.1056/NEJMoa1908075