Trial reportThe New England journal of medicine2018
Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma.
6 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
In one paragraph
Trial report in The New England journal of medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 6 registered trials, which are not on this map. Cited by 1,385 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
1,385citing papers in PubMed, 3 pooled it
137.9field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 3, Randomized, Double-blind, Controlled Study of Cabozantinib (XL184) vs Placebo in Subjects With Hepatocellular Carcinoma Who Have Received Prior Sorafenib
Phase II Trial of Regorafenib in Patients With Unresectable Hepatocellular Carcinoma After Progression on First Line Atezolizumab Plus Bevacizumab (REGONEXT Trial)
A Phase II Study of Cabozantinib for Patients With Recurrent or Progressive Meningioma
Lenalidomide to Reverse Drug Resistance After Lenvatinib Combined With PD-1 Inhibitors in the First-line Treatment of Advanced HCC ：a Prospective, Exploratory, Single-arm, Open-label, Multi-center Clinical Study
NCT06007846 phase2 / phase3recruitingnot on this mapstarted 2023, after this paper: background citation
A Prospective Cohort Study of Single Agent Memantine in Patients With Child-Pugh Score ≥ B7 Cirrhosis and Hepatocellular Carcinoma
NCT06535737 phase2not yet recruitingnot on this mapstarted 2024, after this paper: background citation
A Phase 2, Single Arm Study of Cabozantinib in Patients With Hepatocellular Carcinoma Who Have Received Prior Atezolizumab and Bevacizumab
Who cites it
1,385 citing papers in PubMed, 3 syntheses or guidelines pooled it, 2,297 citations in OpenAlex.
- Cabozantinib and thromboembolism in patients with cancer: a systematic review, meta-analysis, and retrospective study.Blood advances · 2026Pooled it
- Current progress and emerging trends of car-based immunotherapy for hepatocellular carcinoma: a data-driven atlas from multidatabase integration.Frontiers in immunology · 2026Pooled it
- Efficacy of immune-based combinations across treatment lines in advanced hepatocellular carcinoma: a systematic review and network meta-analysis.Frontiers in pharmacology · 2026Pooled it
- Clinical Trial: Early Nivolumab Addition to Regorafenib in Patients With Hepatocellular Carcinoma in Second-Line (The GOING Trial).Alimentary pharmacology & therapeutics · 2026Trial
- TACE plus lenvatinib and envafolimab for conversion therapy in unresectable HCC: a prospective pilot study.Frontiers in immunology · 2026Trial
- Anti-PD-L1 envafolimab combined with anti-VEGF suvemcitug in pretreated solid tumors and hepatocellular carcinoma: an open-label phase II study with safety run-in stage.Investigational new drugs · 2025Trial
- Patient characteristics to guide personalized treatment decisions and prognostication in hepatocellular carcinoma.Hepatic oncology · 2026Review
- Systemic treatment paradigms for unresectable and advanced hepatocellular carcinoma in Europe.The Lancet regional health. Europe · 2026Review
- Cabozantinib-associated therapy-refractory lower-leg ulcers in metastatic renal cell carcinoma.JAAD case reports · 2026Article
- Response evaluation to systemic therapy in HCC: Current challenges and future perspectives.Hepatology (Baltimore, Md.) · 2026Review
- Systemic Therapy for Advanced Hepatocellular Carcinoma with Impaired Liver Function: Navigating the Evidence Gap.Cancers · 2026Review
- AI-Powered Marine Drug Discovery: A Putative Dual c-Met/VEGFR2 Lead Candidate for Hepatocellular Carcinoma via Deep Learning and Multiscale Simulation.Current issues in molecular biology · 2026Article
- Regorafenib as Second-Line Versus Later-Line Therapy in Advanced Hepatocellular Carcinoma: A Multicenter Real-World Study with Exploratory Analysis of Prior Immune Checkpoint Inhibitor Exposure.Targeted oncology · 2026Article
- Cabozantinib for Hepatocellular Carcinoma in Real-World Practice (CLERANCE): A Prospective, Interventional Study.Liver cancer · 2026Article
- Article
- 1D228 Attenuates Sorafenib Resistance in Renal Cell Carcinoma Models by Dual Targeting c-Met and AXL.Cells · 2026Article
- C-MET tyrosine kinase receptor: mechanisms, clinical applications and future perspectives in cancer therapy.Signal transduction and targeted therapy · 2026Review
- Cirrhosis, portal hypertension and hepatocellular carcinoma: a stage-based approach.Nature reviews. Gastroenterology & hepatology · 2026Review
- Evolving Landscape of Systemic Therapy for Hepatocellular Carcinoma: From Targeted Therapy and Combination Strategies to Emerging Therapies.Biomedicines · 2026Review
- Tumor Microenvironment-on-a-Chip: Construction and Application in Traditional Chinese Medicine Anti-Tumor Therapy.Biosensors · 2026Review
1,325 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
22 authors at 17 institutions in 9 countries.
Ghassan K Abou-AlfaFrom 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.).
Tim MeyerFrom 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.).
Ann-Lii ChengFrom 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.).
Anthony B El-KhoueiryFrom 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.).
Lorenza RimassaFrom 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.).
Baek-Yeol RyooFrom 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.).
Irfan CicinFrom 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.).
Philippe MerleFrom 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.).
YenHsun ChenFrom 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.).
Joong-Won ParkFrom 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.).
Jean-Frederic BlancFrom 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.).
Luigi BolondiFrom 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.).
Heinz-Josef KlümpenFrom 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.).
Stephen L ChanFrom 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.).
Vittorina ZagonelFrom 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.).
Tiziana PressianiFrom 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.).
Min-Hee RyuFrom 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.).
Alan P VenookFrom 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.).
Colin HesselFrom 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.).
Anne E Borgman-HageyFrom 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.).
Gisela SchwabFrom 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.).
Robin K KelleyFrom 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.).
Exelixis (United States) · USUCSF Helen Diller Family Comprehensive Cancer Center · USAcademic Medical Center · NLAsan Medical Center · KRCentre Hospitalier Universitaire de Bordeaux · FRChi Mei Medical Center · TWChinese University of Hong Kong · CNHôpital Lyon Sud · FRIstituti di Ricovero e Cura a Carattere Scientifico · ITMemorial Sloan Kettering Cancer Center · USNational Cancer Center · KRNational Taiwan University Hospital · TWTrakya University · TRUlsan College · KRUniversity College London · GBUniversity of Bologna · ITUSC Norris Comprehensive Cancer Center · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4MUSC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4MNCI NIH HHS P30 CA008748NCI NIH HHS P30 CA014089
Abstract
backgroundCabozantinib 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.
methodsA 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.
resultsAt 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%).
conclusionsAmong 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 .).
Indexed as
AdultAgedAged, 80 and overAnilidesAntineoplastic AgentsCarcinoma, HepatocellularDisease-Free SurvivalDouble-Blind MethodFemaleHumansKaplan-Meier EstimateLiver NeoplasmsMaleMiddle AgedPyridinesReceptor Protein-Tyrosine KinasesAnilidesAntineoplastic AgentscabozantinibPyridinesReceptor Protein-Tyrosine Kinases
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Registered trials
NCT01908426ClinicalTrials.gov
NCT05134532ClinicalTrials.gov
NCT05425004ClinicalTrials.gov
NCT05831969ClinicalTrials.gov
NCT06007846ClinicalTrials.gov
NCT06535737ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.