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PMID: 29972759 Published · ppublish English Clinical Trial, Phase III Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma.

The New England journal of medicine ·Vol. 379 ·No. 1 ·2018-07-05 ·Pages 54-63

Abou-Alfa GK, Meyer T, Cheng AL, El-Khoueiry AB, Rimassa L, Ryoo BY, Cicin I, Merle P, Chen Y, Park JW, Blanc JF, Bolondi L, Klümpen HJ, Chan SL, Zagonel V, Pressiani T, Ryu MH, Venook AP, Hessel C, Borgman-Hagey AE, Schwab G, Kelley RK

Abstract

Cabozantinib inhibits tyrosine kinases, including vascular endothelial growth factor receptors 1, 2, and 3, MET, and AXL, which are implicated in the progression of hepatocellular carcinoma and the development of resistance to sorafenib, the standard initial treatment for advanced disease. This randomized, double-blind, phase 3 trial evaluated cabozantinib as compared with placebo in previously treated patients with advanced hepatocellular carcinoma. A total of 707 patients were randomly assigned in a 2:1 ratio to receive cabozantinib (60 mg once daily) or matching placebo. Eligible patients had received previous treatment with sorafenib, had disease progression after at least one systemic treatment for hepatocellular carcinoma, and may have received up to two previous systemic regimens for advanced hepatocellular carcinoma. The primary end point was overall survival. Secondary end points were progression-free survival and the objective response rate. At the second planned interim analysis, the trial showed significantly longer overall survival with cabozantinib than with placebo. Median overall survival was 10.2 months with cabozantinib and 8.0 months with placebo (hazard ratio for death, 0.76; 95% confidence interval [CI], 0.63 to 0.92; P=0.005). Median progression-free survival was 5.2 months with cabozantinib and 1.9 months with placebo (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.52; P<0.001), and the objective response rates were 4% and less than 1%, respectively (P=0.009). Grade 3 or 4 adverse events occurred in 68% of patients in the cabozantinib group and in 36% in the placebo group. The most common high-grade events were palmar-plantar erythrodysesthesia (17% with cabozantinib vs. 0% with placebo), hypertension (16% vs. 2%), increased aspartate aminotransferase level (12% vs. 7%), fatigue (10% vs. 4%), and diarrhea (10% vs. 2%). Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo. The rate of high-grade adverse events in the cabozantinib group was approximately twice that observed in the placebo group. (Funded by Exelixis; CELESTIAL ClinicalTrials.gov number, NCT01908426 .).

MeSH Terms
Adult Aged Aged, 80 and over Anilides/adverse effects,therapeutic use Antineoplastic Agents/adverse effects,therapeutic use Carcinoma, Hepatocellular/drug therapy Disease-Free Survival Double-Blind Method Female Humans Kaplan-Meier Estimate Liver Neoplasms/drug therapy Male Middle Aged Pyridines/adverse effects,therapeutic use Receptor Protein-Tyrosine Kinases/antagonists & inhibitors
Chemicals
Anilides Antineoplastic Agents Pyridines cabozantinib Receptor Protein-Tyrosine Kinases
Authors & Affiliations
22 authors, click to expand affiliations / ORCID
Abou-Alfa Ghassan K
From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (G.K.A.-A.); Royal Free Hospital and University College London, London (T.M.); National Taiwan University Hospital, Taipei (A.-L.C.), and the Department of Medical Oncology, Liouying Chi Mei Hospital, Tainan (Y.C.) - both in Taiwan; USC Norris Comprehensive Cancer Center, Los Angeles (A.B.E.-K.), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco (A.P.V., R.K.K.), and Exelixis, Alameda (C.H., A.E.B.-H., G.S.) - all in California; Humanitas Cancer Center, Humanitas Clinical and Research Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano (L.R., T.P.), the Department of Medical and Surgical Sciences, University of Bologna, Bologna (L.B.), and Medical Oncology Unit 1, Istituto Oncologico Veneto, IRCCS, Padua (V.Z.) - all in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul (B.-Y.R., M.-H.R.), and the National Cancer Center, Goyang (J.-W.P.) - both in South Korea; Trakya University School of Medicine, Edirne, Turkey (I.C.); Groupement Hospitalier Nord, Lyon (P.M.), and Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Bordeaux (J.-F.B.) - both in France; the Department of Medical Oncology, Academic Medical Center, Amsterdam (H.-J.K.); and the Chinese University of Hong Kong, State Key Laboratory in Oncology in South China, Hong Kong (S.L.C.).
Meyer Tim
From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (G.K.A.-A.); Royal Free Hospital and University College London, London (T.M.); National Taiwan University Hospital, Taipei (A.-L.C.), and the Department of Medical Oncology, Liouying Chi Mei Hospital, Tainan (Y.C.) - both in Taiwan; USC Norris Comprehensive Cancer Center, Los Angeles (A.B.E.-K.), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco (A.P.V., R.K.K.), and Exelixis, Alameda (C.H., A.E.B.-H., G.S.) - all in California; Humanitas Cancer Center, Humanitas Clinical and Research Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano (L.R., T.P.), the Department of Medical and Surgical Sciences, University of Bologna, Bologna (L.B.), and Medical Oncology Unit 1, Istituto Oncologico Veneto, IRCCS, Padua (V.Z.) - all in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul (B.-Y.R., M.-H.R.), and the National Cancer Center, Goyang (J.-W.P.) - both in South Korea; Trakya University School of Medicine, Edirne, Turkey (I.C.); Groupement Hospitalier Nord, Lyon (P.M.), and Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Bordeaux (J.-F.B.) - both in France; the Department of Medical Oncology, Academic Medical Center, Amsterdam (H.-J.K.); and the Chinese University of Hong Kong, State Key Laboratory in Oncology in South China, Hong Kong (S.L.C.).
Cheng Ann-Lii
From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (G.K.A.-A.); Royal Free Hospital and University College London, London (T.M.); National Taiwan University Hospital, Taipei (A.-L.C.), and the Department of Medical Oncology, Liouying Chi Mei Hospital, Tainan (Y.C.) - both in Taiwan; USC Norris Comprehensive Cancer Center, Los Angeles (A.B.E.-K.), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco (A.P.V., R.K.K.), and Exelixis, Alameda (C.H., A.E.B.-H., G.S.) - all in California; Humanitas Cancer Center, Humanitas Clinical and Research Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano (L.R., T.P.), the Department of Medical and Surgical Sciences, University of Bologna, Bologna (L.B.), and Medical Oncology Unit 1, Istituto Oncologico Veneto, IRCCS, Padua (V.Z.) - all in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul (B.-Y.R., M.-H.R.), and the National Cancer Center, Goyang (J.-W.P.) - both in South Korea; Trakya University School of Medicine, Edirne, Turkey (I.C.); Groupement Hospitalier Nord, Lyon (P.M.), and Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Bordeaux (J.-F.B.) - both in France; the Department of Medical Oncology, Academic Medical Center, Amsterdam (H.-J.K.); and the Chinese University of Hong Kong, State Key Laboratory in Oncology in South China, Hong Kong (S.L.C.).
El-Khoueiry Anthony B
From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (G.K.A.-A.); Royal Free Hospital and University College London, London (T.M.); National Taiwan University Hospital, Taipei (A.-L.C.), and the Department of Medical Oncology, Liouying Chi Mei Hospital, Tainan (Y.C.) - both in Taiwan; USC Norris Comprehensive Cancer Center, Los Angeles (A.B.E.-K.), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco (A.P.V., R.K.K.), and Exelixis, Alameda (C.H., A.E.B.-H., G.S.) - all in California; Humanitas Cancer Center, Humanitas Clinical and Research Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano (L.R., T.P.), the Department of Medical and Surgical Sciences, University of Bologna, Bologna (L.B.), and Medical Oncology Unit 1, Istituto Oncologico Veneto, IRCCS, Padua (V.Z.) - all in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul (B.-Y.R., M.-H.R.), and the National Cancer Center, Goyang (J.-W.P.) - both in South Korea; Trakya University School of Medicine, Edirne, Turkey (I.C.); Groupement Hospitalier Nord, Lyon (P.M.), and Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Bordeaux (J.-F.B.) - both in France; the Department of Medical Oncology, Academic Medical Center, Amsterdam (H.-J.K.); and the Chinese University of Hong Kong, State Key Laboratory in Oncology in South China, Hong Kong (S.L.C.).
Rimassa Lorenza
From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (G.K.A.-A.); Royal Free Hospital and University College London, London (T.M.); National Taiwan University Hospital, Taipei (A.-L.C.), and the Department of Medical Oncology, Liouying Chi Mei Hospital, Tainan (Y.C.) - both in Taiwan; USC Norris Comprehensive Cancer Center, Los Angeles (A.B.E.-K.), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco (A.P.V., R.K.K.), and Exelixis, Alameda (C.H., A.E.B.-H., G.S.) - all in California; Humanitas Cancer Center, Humanitas Clinical and Research Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano (L.R., T.P.), the Department of Medical and Surgical Sciences, University of Bologna, Bologna (L.B.), and Medical Oncology Unit 1, Istituto Oncologico Veneto, IRCCS, Padua (V.Z.) - all in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul (B.-Y.R., M.-H.R.), and the National Cancer Center, Goyang (J.-W.P.) - both in South Korea; Trakya University School of Medicine, Edirne, Turkey (I.C.); Groupement Hospitalier Nord, Lyon (P.M.), and Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Bordeaux (J.-F.B.) - both in France; the Department of Medical Oncology, Academic Medical Center, Amsterdam (H.-J.K.); and the Chinese University of Hong Kong, State Key Laboratory in Oncology in South China, Hong Kong (S.L.C.).
Ryoo Baek-Yeol
From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (G.K.A.-A.); Royal Free Hospital and University College London, London (T.M.); National Taiwan University Hospital, Taipei (A.-L.C.), and the Department of Medical Oncology, Liouying Chi Mei Hospital, Tainan (Y.C.) - both in Taiwan; USC Norris Comprehensive Cancer Center, Los Angeles (A.B.E.-K.), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco (A.P.V., R.K.K.), and Exelixis, Alameda (C.H., A.E.B.-H., G.S.) - all in California; Humanitas Cancer Center, Humanitas Clinical and Research Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano (L.R., T.P.), the Department of Medical and Surgical Sciences, University of Bologna, Bologna (L.B.), and Medical Oncology Unit 1, Istituto Oncologico Veneto, IRCCS, Padua (V.Z.) - all in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul (B.-Y.R., M.-H.R.), and the National Cancer Center, Goyang (J.-W.P.) - both in South Korea; Trakya University School of Medicine, Edirne, Turkey (I.C.); Groupement Hospitalier Nord, Lyon (P.M.), and Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Bordeaux (J.-F.B.) - both in France; the Department of Medical Oncology, Academic Medical Center, Amsterdam (H.-J.K.); and the Chinese University of Hong Kong, State Key Laboratory in Oncology in South China, Hong Kong (S.L.C.).
Cicin Irfan
From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (G.K.A.-A.); Royal Free Hospital and University College London, London (T.M.); National Taiwan University Hospital, Taipei (A.-L.C.), and the Department of Medical Oncology, Liouying Chi Mei Hospital, Tainan (Y.C.) - both in Taiwan; USC Norris Comprehensive Cancer Center, Los Angeles (A.B.E.-K.), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco (A.P.V., R.K.K.), and Exelixis, Alameda (C.H., A.E.B.-H., G.S.) - all in California; Humanitas Cancer Center, Humanitas Clinical and Research Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano (L.R., T.P.), the Department of Medical and Surgical Sciences, University of Bologna, Bologna (L.B.), and Medical Oncology Unit 1, Istituto Oncologico Veneto, IRCCS, Padua (V.Z.) - all in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul (B.-Y.R., M.-H.R.), and the National Cancer Center, Goyang (J.-W.P.) - both in South Korea; Trakya University School of Medicine, Edirne, Turkey (I.C.); Groupement Hospitalier Nord, Lyon (P.M.), and Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Bordeaux (J.-F.B.) - both in France; the Department of Medical Oncology, Academic Medical Center, Amsterdam (H.-J.K.); and the Chinese University of Hong Kong, State Key Laboratory in Oncology in South China, Hong Kong (S.L.C.).
Merle Philippe
From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (G.K.A.-A.); Royal Free Hospital and University College London, London (T.M.); National Taiwan University Hospital, Taipei (A.-L.C.), and the Department of Medical Oncology, Liouying Chi Mei Hospital, Tainan (Y.C.) - both in Taiwan; USC Norris Comprehensive Cancer Center, Los Angeles (A.B.E.-K.), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco (A.P.V., R.K.K.), and Exelixis, Alameda (C.H., A.E.B.-H., G.S.) - all in California; Humanitas Cancer Center, Humanitas Clinical and Research Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano (L.R., T.P.), the Department of Medical and Surgical Sciences, University of Bologna, Bologna (L.B.), and Medical Oncology Unit 1, Istituto Oncologico Veneto, IRCCS, Padua (V.Z.) - all in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul (B.-Y.R., M.-H.R.), and the National Cancer Center, Goyang (J.-W.P.) - both in South Korea; Trakya University School of Medicine, Edirne, Turkey (I.C.); Groupement Hospitalier Nord, Lyon (P.M.), and Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Bordeaux (J.-F.B.) - both in France; the Department of Medical Oncology, Academic Medical Center, Amsterdam (H.-J.K.); and the Chinese University of Hong Kong, State Key Laboratory in Oncology in South China, Hong Kong (S.L.C.).
Chen YenHsun
From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (G.K.A.-A.); Royal Free Hospital and University College London, London (T.M.); National Taiwan University Hospital, Taipei (A.-L.C.), and the Department of Medical Oncology, Liouying Chi Mei Hospital, Tainan (Y.C.) - both in Taiwan; USC Norris Comprehensive Cancer Center, Los Angeles (A.B.E.-K.), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco (A.P.V., R.K.K.), and Exelixis, Alameda (C.H., A.E.B.-H., G.S.) - all in California; Humanitas Cancer Center, Humanitas Clinical and Research Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano (L.R., T.P.), the Department of Medical and Surgical Sciences, University of Bologna, Bologna (L.B.), and Medical Oncology Unit 1, Istituto Oncologico Veneto, IRCCS, Padua (V.Z.) - all in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul (B.-Y.R., M.-H.R.), and the National Cancer Center, Goyang (J.-W.P.) - both in South Korea; Trakya University School of Medicine, Edirne, Turkey (I.C.); Groupement Hospitalier Nord, Lyon (P.M.), and Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Bordeaux (J.-F.B.) - both in France; the Department of Medical Oncology, Academic Medical Center, Amsterdam (H.-J.K.); and the Chinese University of Hong Kong, State Key Laboratory in Oncology in South China, Hong Kong (S.L.C.).
Park Joong-Won
From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (G.K.A.-A.); Royal Free Hospital and University College London, London (T.M.); National Taiwan University Hospital, Taipei (A.-L.C.), and the Department of Medical Oncology, Liouying Chi Mei Hospital, Tainan (Y.C.) - both in Taiwan; USC Norris Comprehensive Cancer Center, Los Angeles (A.B.E.-K.), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco (A.P.V., R.K.K.), and Exelixis, Alameda (C.H., A.E.B.-H., G.S.) - all in California; Humanitas Cancer Center, Humanitas Clinical and Research Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano (L.R., T.P.), the Department of Medical and Surgical Sciences, University of Bologna, Bologna (L.B.), and Medical Oncology Unit 1, Istituto Oncologico Veneto, IRCCS, Padua (V.Z.) - all in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul (B.-Y.R., M.-H.R.), and the National Cancer Center, Goyang (J.-W.P.) - both in South Korea; Trakya University School of Medicine, Edirne, Turkey (I.C.); Groupement Hospitalier Nord, Lyon (P.M.), and Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Bordeaux (J.-F.B.) - both in France; the Department of Medical Oncology, Academic Medical Center, Amsterdam (H.-J.K.); and the Chinese University of Hong Kong, State Key Laboratory in Oncology in South China, Hong Kong (S.L.C.).
Blanc Jean-Frederic
From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (G.K.A.-A.); Royal Free Hospital and University College London, London (T.M.); National Taiwan University Hospital, Taipei (A.-L.C.), and the Department of Medical Oncology, Liouying Chi Mei Hospital, Tainan (Y.C.) - both in Taiwan; USC Norris Comprehensive Cancer Center, Los Angeles (A.B.E.-K.), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco (A.P.V., R.K.K.), and Exelixis, Alameda (C.H., A.E.B.-H., G.S.) - all in California; Humanitas Cancer Center, Humanitas Clinical and Research Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano (L.R., T.P.), the Department of Medical and Surgical Sciences, University of Bologna, Bologna (L.B.), and Medical Oncology Unit 1, Istituto Oncologico Veneto, IRCCS, Padua (V.Z.) - all in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul (B.-Y.R., M.-H.R.), and the National Cancer Center, Goyang (J.-W.P.) - both in South Korea; Trakya University School of Medicine, Edirne, Turkey (I.C.); Groupement Hospitalier Nord, Lyon (P.M.), and Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Bordeaux (J.-F.B.) - both in France; the Department of Medical Oncology, Academic Medical Center, Amsterdam (H.-J.K.); and the Chinese University of Hong Kong, State Key Laboratory in Oncology in South China, Hong Kong (S.L.C.).
Bolondi Luigi
From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (G.K.A.-A.); Royal Free Hospital and University College London, London (T.M.); National Taiwan University Hospital, Taipei (A.-L.C.), and the Department of Medical Oncology, Liouying Chi Mei Hospital, Tainan (Y.C.) - both in Taiwan; USC Norris Comprehensive Cancer Center, Los Angeles (A.B.E.-K.), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco (A.P.V., R.K.K.), and Exelixis, Alameda (C.H., A.E.B.-H., G.S.) - all in California; Humanitas Cancer Center, Humanitas Clinical and Research Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano (L.R., T.P.), the Department of Medical and Surgical Sciences, University of Bologna, Bologna (L.B.), and Medical Oncology Unit 1, Istituto Oncologico Veneto, IRCCS, Padua (V.Z.) - all in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul (B.-Y.R., M.-H.R.), and the National Cancer Center, Goyang (J.-W.P.) - both in South Korea; Trakya University School of Medicine, Edirne, Turkey (I.C.); Groupement Hospitalier Nord, Lyon (P.M.), and Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Bordeaux (J.-F.B.) - both in France; the Department of Medical Oncology, Academic Medical Center, Amsterdam (H.-J.K.); and the Chinese University of Hong Kong, State Key Laboratory in Oncology in South China, Hong Kong (S.L.C.).
Klümpen Heinz-Josef
From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (G.K.A.-A.); Royal Free Hospital and University College London, London (T.M.); National Taiwan University Hospital, Taipei (A.-L.C.), and the Department of Medical Oncology, Liouying Chi Mei Hospital, Tainan (Y.C.) - both in Taiwan; USC Norris Comprehensive Cancer Center, Los Angeles (A.B.E.-K.), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco (A.P.V., R.K.K.), and Exelixis, Alameda (C.H., A.E.B.-H., G.S.) - all in California; Humanitas Cancer Center, Humanitas Clinical and Research Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano (L.R., T.P.), the Department of Medical and Surgical Sciences, University of Bologna, Bologna (L.B.), and Medical Oncology Unit 1, Istituto Oncologico Veneto, IRCCS, Padua (V.Z.) - all in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul (B.-Y.R., M.-H.R.), and the National Cancer Center, Goyang (J.-W.P.) - both in South Korea; Trakya University School of Medicine, Edirne, Turkey (I.C.); Groupement Hospitalier Nord, Lyon (P.M.), and Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Bordeaux (J.-F.B.) - both in France; the Department of Medical Oncology, Academic Medical Center, Amsterdam (H.-J.K.); and the Chinese University of Hong Kong, State Key Laboratory in Oncology in South China, Hong Kong (S.L.C.).
Chan Stephen L
From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (G.K.A.-A.); Royal Free Hospital and University College London, London (T.M.); National Taiwan University Hospital, Taipei (A.-L.C.), and the Department of Medical Oncology, Liouying Chi Mei Hospital, Tainan (Y.C.) - both in Taiwan; USC Norris Comprehensive Cancer Center, Los Angeles (A.B.E.-K.), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco (A.P.V., R.K.K.), and Exelixis, Alameda (C.H., A.E.B.-H., G.S.) - all in California; Humanitas Cancer Center, Humanitas Clinical and Research Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano (L.R., T.P.), the Department of Medical and Surgical Sciences, University of Bologna, Bologna (L.B.), and Medical Oncology Unit 1, Istituto Oncologico Veneto, IRCCS, Padua (V.Z.) - all in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul (B.-Y.R., M.-H.R.), and the National Cancer Center, Goyang (J.-W.P.) - both in South Korea; Trakya University School of Medicine, Edirne, Turkey (I.C.); Groupement Hospitalier Nord, Lyon (P.M.), and Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Bordeaux (J.-F.B.) - both in France; the Department of Medical Oncology, Academic Medical Center, Amsterdam (H.-J.K.); and the Chinese University of Hong Kong, State Key Laboratory in Oncology in South China, Hong Kong (S.L.C.).
Zagonel Vittorina
From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (G.K.A.-A.); Royal Free Hospital and University College London, London (T.M.); National Taiwan University Hospital, Taipei (A.-L.C.), and the Department of Medical Oncology, Liouying Chi Mei Hospital, Tainan (Y.C.) - both in Taiwan; USC Norris Comprehensive Cancer Center, Los Angeles (A.B.E.-K.), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco (A.P.V., R.K.K.), and Exelixis, Alameda (C.H., A.E.B.-H., G.S.) - all in California; Humanitas Cancer Center, Humanitas Clinical and Research Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano (L.R., T.P.), the Department of Medical and Surgical Sciences, University of Bologna, Bologna (L.B.), and Medical Oncology Unit 1, Istituto Oncologico Veneto, IRCCS, Padua (V.Z.) - all in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul (B.-Y.R., M.-H.R.), and the National Cancer Center, Goyang (J.-W.P.) - both in South Korea; Trakya University School of Medicine, Edirne, Turkey (I.C.); Groupement Hospitalier Nord, Lyon (P.M.), and Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Bordeaux (J.-F.B.) - both in France; the Department of Medical Oncology, Academic Medical Center, Amsterdam (H.-J.K.); and the Chinese University of Hong Kong, State Key Laboratory in Oncology in South China, Hong Kong (S.L.C.).
Pressiani Tiziana
From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (G.K.A.-A.); Royal Free Hospital and University College London, London (T.M.); National Taiwan University Hospital, Taipei (A.-L.C.), and the Department of Medical Oncology, Liouying Chi Mei Hospital, Tainan (Y.C.) - both in Taiwan; USC Norris Comprehensive Cancer Center, Los Angeles (A.B.E.-K.), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco (A.P.V., R.K.K.), and Exelixis, Alameda (C.H., A.E.B.-H., G.S.) - all in California; Humanitas Cancer Center, Humanitas Clinical and Research Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano (L.R., T.P.), the Department of Medical and Surgical Sciences, University of Bologna, Bologna (L.B.), and Medical Oncology Unit 1, Istituto Oncologico Veneto, IRCCS, Padua (V.Z.) - all in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul (B.-Y.R., M.-H.R.), and the National Cancer Center, Goyang (J.-W.P.) - both in South Korea; Trakya University School of Medicine, Edirne, Turkey (I.C.); Groupement Hospitalier Nord, Lyon (P.M.), and Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Bordeaux (J.-F.B.) - both in France; the Department of Medical Oncology, Academic Medical Center, Amsterdam (H.-J.K.); and the Chinese University of Hong Kong, State Key Laboratory in Oncology in South China, Hong Kong (S.L.C.).
Ryu Min-Hee
From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (G.K.A.-A.); Royal Free Hospital and University College London, London (T.M.); National Taiwan University Hospital, Taipei (A.-L.C.), and the Department of Medical Oncology, Liouying Chi Mei Hospital, Tainan (Y.C.) - both in Taiwan; USC Norris Comprehensive Cancer Center, Los Angeles (A.B.E.-K.), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco (A.P.V., R.K.K.), and Exelixis, Alameda (C.H., A.E.B.-H., G.S.) - all in California; Humanitas Cancer Center, Humanitas Clinical and Research Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano (L.R., T.P.), the Department of Medical and Surgical Sciences, University of Bologna, Bologna (L.B.), and Medical Oncology Unit 1, Istituto Oncologico Veneto, IRCCS, Padua (V.Z.) - all in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul (B.-Y.R., M.-H.R.), and the National Cancer Center, Goyang (J.-W.P.) - both in South Korea; Trakya University School of Medicine, Edirne, Turkey (I.C.); Groupement Hospitalier Nord, Lyon (P.M.), and Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Bordeaux (J.-F.B.) - both in France; the Department of Medical Oncology, Academic Medical Center, Amsterdam (H.-J.K.); and the Chinese University of Hong Kong, State Key Laboratory in Oncology in South China, Hong Kong (S.L.C.).
Venook Alan P
From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (G.K.A.-A.); Royal Free Hospital and University College London, London (T.M.); National Taiwan University Hospital, Taipei (A.-L.C.), and the Department of Medical Oncology, Liouying Chi Mei Hospital, Tainan (Y.C.) - both in Taiwan; USC Norris Comprehensive Cancer Center, Los Angeles (A.B.E.-K.), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco (A.P.V., R.K.K.), and Exelixis, Alameda (C.H., A.E.B.-H., G.S.) - all in California; Humanitas Cancer Center, Humanitas Clinical and Research Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano (L.R., T.P.), the Department of Medical and Surgical Sciences, University of Bologna, Bologna (L.B.), and Medical Oncology Unit 1, Istituto Oncologico Veneto, IRCCS, Padua (V.Z.) - all in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul (B.-Y.R., M.-H.R.), and the National Cancer Center, Goyang (J.-W.P.) - both in South Korea; Trakya University School of Medicine, Edirne, Turkey (I.C.); Groupement Hospitalier Nord, Lyon (P.M.), and Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Bordeaux (J.-F.B.) - both in France; the Department of Medical Oncology, Academic Medical Center, Amsterdam (H.-J.K.); and the Chinese University of Hong Kong, State Key Laboratory in Oncology in South China, Hong Kong (S.L.C.).
Hessel Colin
From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (G.K.A.-A.); Royal Free Hospital and University College London, London (T.M.); National Taiwan University Hospital, Taipei (A.-L.C.), and the Department of Medical Oncology, Liouying Chi Mei Hospital, Tainan (Y.C.) - both in Taiwan; USC Norris Comprehensive Cancer Center, Los Angeles (A.B.E.-K.), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco (A.P.V., R.K.K.), and Exelixis, Alameda (C.H., A.E.B.-H., G.S.) - all in California; Humanitas Cancer Center, Humanitas Clinical and Research Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano (L.R., T.P.), the Department of Medical and Surgical Sciences, University of Bologna, Bologna (L.B.), and Medical Oncology Unit 1, Istituto Oncologico Veneto, IRCCS, Padua (V.Z.) - all in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul (B.-Y.R., M.-H.R.), and the National Cancer Center, Goyang (J.-W.P.) - both in South Korea; Trakya University School of Medicine, Edirne, Turkey (I.C.); Groupement Hospitalier Nord, Lyon (P.M.), and Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Bordeaux (J.-F.B.) - both in France; the Department of Medical Oncology, Academic Medical Center, Amsterdam (H.-J.K.); and the Chinese University of Hong Kong, State Key Laboratory in Oncology in South China, Hong Kong (S.L.C.).
Borgman-Hagey Anne E
From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (G.K.A.-A.); Royal Free Hospital and University College London, London (T.M.); National Taiwan University Hospital, Taipei (A.-L.C.), and the Department of Medical Oncology, Liouying Chi Mei Hospital, Tainan (Y.C.) - both in Taiwan; USC Norris Comprehensive Cancer Center, Los Angeles (A.B.E.-K.), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco (A.P.V., R.K.K.), and Exelixis, Alameda (C.H., A.E.B.-H., G.S.) - all in California; Humanitas Cancer Center, Humanitas Clinical and Research Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano (L.R., T.P.), the Department of Medical and Surgical Sciences, University of Bologna, Bologna (L.B.), and Medical Oncology Unit 1, Istituto Oncologico Veneto, IRCCS, Padua (V.Z.) - all in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul (B.-Y.R., M.-H.R.), and the National Cancer Center, Goyang (J.-W.P.) - both in South Korea; Trakya University School of Medicine, Edirne, Turkey (I.C.); Groupement Hospitalier Nord, Lyon (P.M.), and Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Bordeaux (J.-F.B.) - both in France; the Department of Medical Oncology, Academic Medical Center, Amsterdam (H.-J.K.); and the Chinese University of Hong Kong, State Key Laboratory in Oncology in South China, Hong Kong (S.L.C.).
Schwab Gisela
From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (G.K.A.-A.); Royal Free Hospital and University College London, London (T.M.); National Taiwan University Hospital, Taipei (A.-L.C.), and the Department of Medical Oncology, Liouying Chi Mei Hospital, Tainan (Y.C.) - both in Taiwan; USC Norris Comprehensive Cancer Center, Los Angeles (A.B.E.-K.), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco (A.P.V., R.K.K.), and Exelixis, Alameda (C.H., A.E.B.-H., G.S.) - all in California; Humanitas Cancer Center, Humanitas Clinical and Research Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano (L.R., T.P.), the Department of Medical and Surgical Sciences, University of Bologna, Bologna (L.B.), and Medical Oncology Unit 1, Istituto Oncologico Veneto, IRCCS, Padua (V.Z.) - all in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul (B.-Y.R., M.-H.R.), and the National Cancer Center, Goyang (J.-W.P.) - both in South Korea; Trakya University School of Medicine, Edirne, Turkey (I.C.); Groupement Hospitalier Nord, Lyon (P.M.), and Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Bordeaux (J.-F.B.) - both in France; the Department of Medical Oncology, Academic Medical Center, Amsterdam (H.-J.K.); and the Chinese University of Hong Kong, State Key Laboratory in Oncology in South China, Hong Kong (S.L.C.).
Kelley Robin K
From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (G.K.A.-A.); Royal Free Hospital and University College London, London (T.M.); National Taiwan University Hospital, Taipei (A.-L.C.), and the Department of Medical Oncology, Liouying Chi Mei Hospital, Tainan (Y.C.) - both in Taiwan; USC Norris Comprehensive Cancer Center, Los Angeles (A.B.E.-K.), UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco (A.P.V., R.K.K.), and Exelixis, Alameda (C.H., A.E.B.-H., G.S.) - all in California; Humanitas Cancer Center, Humanitas Clinical and Research Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Rozzano (L.R., T.P.), the Department of Medical and Surgical Sciences, University of Bologna, Bologna (L.B.), and Medical Oncology Unit 1, Istituto Oncologico Veneto, IRCCS, Padua (V.Z.) - all in Italy; Asan Medical Center, University of Ulsan College of Medicine, Seoul (B.-Y.R., M.-H.R.), and the National Cancer Center, Goyang (J.-W.P.) - both in South Korea; Trakya University School of Medicine, Edirne, Turkey (I.C.); Groupement Hospitalier Nord, Lyon (P.M.), and Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Bordeaux (J.-F.B.) - both in France; the Department of Medical Oncology, Academic Medical Center, Amsterdam (H.-J.K.); and the Chinese University of Hong Kong, State Key Laboratory in Oncology in South China, Hong Kong (S.L.C.).
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Article Info
Journal
The New England journal of medicine
Abbr.
N Engl J Med
ISSN
1533-4406
DOI
10.1056/NEJMoa1717002
Published
2018-07-05
Pages
54-63
Language
English
Region
United States
NLM ID
0255562
PMCID
PMC7523244
Subset
IM
Grants
NCI NIH HHS · P30 CA014089 · United States
Databases
ClinicalTrials.gov
NCT01908426
Corrections
CommentIn
PMID: 30285325
CommentIn
PMID: 30881965
CommentIn
PMID: 31098366
External Links
PubMed source DOI: 10.1056/NEJMoa1717002 PMC Full Text View journal details
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