Evidence map›Paper›PMID 37163623›Full record

Trial reportThe New England journal of medicine2023

Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma.

Toni K Choueiri, Thomas Powles, Laurence Albiges, Mauricio Burotto, Cezary Szczylik, Bogdan Zurawski, Eduardo Yanez Ruiz, Marco Maruzzo, Alberto Suarez Zaizar, Luis E Fein and 9 more

Registry-linked trialOpen access · greenAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The New England journal of medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03937219 (A Randomized, Double-Blind, Controlled Phase 3 Study of Cabozantinib in Combination With Nivolumab and Ipilimumab Versus Nivolumab and Ipilimumab in Subjects With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma of Intermediate or Poor Risk), which is not on this map. Cited by 103 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed, 9 pooled it
37.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

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.

2 · The registry

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.

NCT03937219 phase3active not recruitingnot on this map

A Randomized, Double-Blind, Controlled Phase 3 Study of Cabozantinib in Combination With Nivolumab and Ipilimumab Versus Nivolumab and Ipilimumab in Subjects With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma of Intermediate or Poor Risk

TypeinterventionalSponsorExelixisRan2019 to 2027Enrolled855ConditionsRenal Cell CarcinomaArmsCabozantinib, Nivolumab, Ipilimumab, Cabozantinib-matched placebo
3 · Its place in the literature

Who cites it

103 citing papers in PubMed, 9 syntheses or guidelines pooled it, 144 citations in OpenAlex.

  1. Pooled it
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  4. Guideline
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  10. Trial
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  18. Beyond mBiomedicines · 2026
    Review
  19. Review
  20. Target identification and assessment in the era of AI.Nature reviews. Drug discovery · 2026
    Review

43 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 7 institutions in 10 countries.

Toni K ChoueiriFrom the Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School - both in Boston (T.K.C.); the Department of Genitourinary Oncology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free NHS Trust, London (T.P.); the Department of Cancer Medicine, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France (L.A.); Bradford Hill Clinical Research Center, Santiago (M.B.), and James Lind Centro de Investigación del Cáncer, Temuco (E.Y.R.) - both in Chile; the Postgraduate Medical Center, Department of Oncology, European Health Center, Otwock, Warsaw (C. Szczylik), and the Department of Outpatient Chemotherapy, Professor Franciszek Łukaszczyk Oncology Center, Bydgoszcz (B.Z.) - both in Poland; Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IRCCS, Padua, Italy (M.M.); Consultorio de Medicina Especializada, Benito Juárez, Mexico City (A.S.Z.); Instituto de Oncología de Rosario, Rosario, Argentina (L.E.F.); Latin American Cooperative Oncology Group, Porto Alegre, and Beneficência Portuguesa de São Paulo, São Paulo - both in Brazil (F.A.S.); the Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada (D.Y.C.H.); Exelixis, Alameda, CA (F.W., F.M., Y.-L.C.); Bristol Myers Squibb, Boudry, Switzerland (M.K.L.); the Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona (C. Suarez); and the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.J.M.).
Thomas PowlesFrom the Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School - both in Boston (T.K.C.); the Department of Genitourinary Oncology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free NHS Trust, London (T.P.); the Department of Cancer Medicine, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France (L.A.); Bradford Hill Clinical Research Center, Santiago (M.B.), and James Lind Centro de Investigación del Cáncer, Temuco (E.Y.R.) - both in Chile; the Postgraduate Medical Center, Department of Oncology, European Health Center, Otwock, Warsaw (C. Szczylik), and the Department of Outpatient Chemotherapy, Professor Franciszek Łukaszczyk Oncology Center, Bydgoszcz (B.Z.) - both in Poland; Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IRCCS, Padua, Italy (M.M.); Consultorio de Medicina Especializada, Benito Juárez, Mexico City (A.S.Z.); Instituto de Oncología de Rosario, Rosario, Argentina (L.E.F.); Latin American Cooperative Oncology Group, Porto Alegre, and Beneficência Portuguesa de São Paulo, São Paulo - both in Brazil (F.A.S.); the Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada (D.Y.C.H.); Exelixis, Alameda, CA (F.W., F.M., Y.-L.C.); Bristol Myers Squibb, Boudry, Switzerland (M.K.L.); the Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona (C. Suarez); and the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.J.M.).
Laurence AlbigesFrom the Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School - both in Boston (T.K.C.); the Department of Genitourinary Oncology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free NHS Trust, London (T.P.); the Department of Cancer Medicine, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France (L.A.); Bradford Hill Clinical Research Center, Santiago (M.B.), and James Lind Centro de Investigación del Cáncer, Temuco (E.Y.R.) - both in Chile; the Postgraduate Medical Center, Department of Oncology, European Health Center, Otwock, Warsaw (C. Szczylik), and the Department of Outpatient Chemotherapy, Professor Franciszek Łukaszczyk Oncology Center, Bydgoszcz (B.Z.) - both in Poland; Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IRCCS, Padua, Italy (M.M.); Consultorio de Medicina Especializada, Benito Juárez, Mexico City (A.S.Z.); Instituto de Oncología de Rosario, Rosario, Argentina (L.E.F.); Latin American Cooperative Oncology Group, Porto Alegre, and Beneficência Portuguesa de São Paulo, São Paulo - both in Brazil (F.A.S.); the Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada (D.Y.C.H.); Exelixis, Alameda, CA (F.W., F.M., Y.-L.C.); Bristol Myers Squibb, Boudry, Switzerland (M.K.L.); the Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona (C. Suarez); and the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.J.M.).
Mauricio BurottoFrom the Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School - both in Boston (T.K.C.); the Department of Genitourinary Oncology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free NHS Trust, London (T.P.); the Department of Cancer Medicine, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France (L.A.); Bradford Hill Clinical Research Center, Santiago (M.B.), and James Lind Centro de Investigación del Cáncer, Temuco (E.Y.R.) - both in Chile; the Postgraduate Medical Center, Department of Oncology, European Health Center, Otwock, Warsaw (C. Szczylik), and the Department of Outpatient Chemotherapy, Professor Franciszek Łukaszczyk Oncology Center, Bydgoszcz (B.Z.) - both in Poland; Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IRCCS, Padua, Italy (M.M.); Consultorio de Medicina Especializada, Benito Juárez, Mexico City (A.S.Z.); Instituto de Oncología de Rosario, Rosario, Argentina (L.E.F.); Latin American Cooperative Oncology Group, Porto Alegre, and Beneficência Portuguesa de São Paulo, São Paulo - both in Brazil (F.A.S.); the Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada (D.Y.C.H.); Exelixis, Alameda, CA (F.W., F.M., Y.-L.C.); Bristol Myers Squibb, Boudry, Switzerland (M.K.L.); the Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona (C. Suarez); and the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.J.M.).
Cezary SzczylikFrom the Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School - both in Boston (T.K.C.); the Department of Genitourinary Oncology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free NHS Trust, London (T.P.); the Department of Cancer Medicine, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France (L.A.); Bradford Hill Clinical Research Center, Santiago (M.B.), and James Lind Centro de Investigación del Cáncer, Temuco (E.Y.R.) - both in Chile; the Postgraduate Medical Center, Department of Oncology, European Health Center, Otwock, Warsaw (C. Szczylik), and the Department of Outpatient Chemotherapy, Professor Franciszek Łukaszczyk Oncology Center, Bydgoszcz (B.Z.) - both in Poland; Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IRCCS, Padua, Italy (M.M.); Consultorio de Medicina Especializada, Benito Juárez, Mexico City (A.S.Z.); Instituto de Oncología de Rosario, Rosario, Argentina (L.E.F.); Latin American Cooperative Oncology Group, Porto Alegre, and Beneficência Portuguesa de São Paulo, São Paulo - both in Brazil (F.A.S.); the Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada (D.Y.C.H.); Exelixis, Alameda, CA (F.W., F.M., Y.-L.C.); Bristol Myers Squibb, Boudry, Switzerland (M.K.L.); the Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona (C. Suarez); and the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.J.M.).
Bogdan ZurawskiFrom the Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School - both in Boston (T.K.C.); the Department of Genitourinary Oncology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free NHS Trust, London (T.P.); the Department of Cancer Medicine, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France (L.A.); Bradford Hill Clinical Research Center, Santiago (M.B.), and James Lind Centro de Investigación del Cáncer, Temuco (E.Y.R.) - both in Chile; the Postgraduate Medical Center, Department of Oncology, European Health Center, Otwock, Warsaw (C. Szczylik), and the Department of Outpatient Chemotherapy, Professor Franciszek Łukaszczyk Oncology Center, Bydgoszcz (B.Z.) - both in Poland; Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IRCCS, Padua, Italy (M.M.); Consultorio de Medicina Especializada, Benito Juárez, Mexico City (A.S.Z.); Instituto de Oncología de Rosario, Rosario, Argentina (L.E.F.); Latin American Cooperative Oncology Group, Porto Alegre, and Beneficência Portuguesa de São Paulo, São Paulo - both in Brazil (F.A.S.); the Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada (D.Y.C.H.); Exelixis, Alameda, CA (F.W., F.M., Y.-L.C.); Bristol Myers Squibb, Boudry, Switzerland (M.K.L.); the Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona (C. Suarez); and the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.J.M.).
Eduardo Yanez RuizFrom the Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School - both in Boston (T.K.C.); the Department of Genitourinary Oncology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free NHS Trust, London (T.P.); the Department of Cancer Medicine, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France (L.A.); Bradford Hill Clinical Research Center, Santiago (M.B.), and James Lind Centro de Investigación del Cáncer, Temuco (E.Y.R.) - both in Chile; the Postgraduate Medical Center, Department of Oncology, European Health Center, Otwock, Warsaw (C. Szczylik), and the Department of Outpatient Chemotherapy, Professor Franciszek Łukaszczyk Oncology Center, Bydgoszcz (B.Z.) - both in Poland; Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IRCCS, Padua, Italy (M.M.); Consultorio de Medicina Especializada, Benito Juárez, Mexico City (A.S.Z.); Instituto de Oncología de Rosario, Rosario, Argentina (L.E.F.); Latin American Cooperative Oncology Group, Porto Alegre, and Beneficência Portuguesa de São Paulo, São Paulo - both in Brazil (F.A.S.); the Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada (D.Y.C.H.); Exelixis, Alameda, CA (F.W., F.M., Y.-L.C.); Bristol Myers Squibb, Boudry, Switzerland (M.K.L.); the Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona (C. Suarez); and the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.J.M.).
Marco MaruzzoFrom the Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School - both in Boston (T.K.C.); the Department of Genitourinary Oncology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free NHS Trust, London (T.P.); the Department of Cancer Medicine, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France (L.A.); Bradford Hill Clinical Research Center, Santiago (M.B.), and James Lind Centro de Investigación del Cáncer, Temuco (E.Y.R.) - both in Chile; the Postgraduate Medical Center, Department of Oncology, European Health Center, Otwock, Warsaw (C. Szczylik), and the Department of Outpatient Chemotherapy, Professor Franciszek Łukaszczyk Oncology Center, Bydgoszcz (B.Z.) - both in Poland; Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IRCCS, Padua, Italy (M.M.); Consultorio de Medicina Especializada, Benito Juárez, Mexico City (A.S.Z.); Instituto de Oncología de Rosario, Rosario, Argentina (L.E.F.); Latin American Cooperative Oncology Group, Porto Alegre, and Beneficência Portuguesa de São Paulo, São Paulo - both in Brazil (F.A.S.); the Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada (D.Y.C.H.); Exelixis, Alameda, CA (F.W., F.M., Y.-L.C.); Bristol Myers Squibb, Boudry, Switzerland (M.K.L.); the Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona (C. Suarez); and the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.J.M.).
Alberto Suarez ZaizarFrom the Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School - both in Boston (T.K.C.); the Department of Genitourinary Oncology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free NHS Trust, London (T.P.); the Department of Cancer Medicine, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France (L.A.); Bradford Hill Clinical Research Center, Santiago (M.B.), and James Lind Centro de Investigación del Cáncer, Temuco (E.Y.R.) - both in Chile; the Postgraduate Medical Center, Department of Oncology, European Health Center, Otwock, Warsaw (C. Szczylik), and the Department of Outpatient Chemotherapy, Professor Franciszek Łukaszczyk Oncology Center, Bydgoszcz (B.Z.) - both in Poland; Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IRCCS, Padua, Italy (M.M.); Consultorio de Medicina Especializada, Benito Juárez, Mexico City (A.S.Z.); Instituto de Oncología de Rosario, Rosario, Argentina (L.E.F.); Latin American Cooperative Oncology Group, Porto Alegre, and Beneficência Portuguesa de São Paulo, São Paulo - both in Brazil (F.A.S.); the Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada (D.Y.C.H.); Exelixis, Alameda, CA (F.W., F.M., Y.-L.C.); Bristol Myers Squibb, Boudry, Switzerland (M.K.L.); the Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona (C. Suarez); and the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.J.M.).ORCID 0000-0001-8506-2224
Luis E FeinFrom the Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School - both in Boston (T.K.C.); the Department of Genitourinary Oncology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free NHS Trust, London (T.P.); the Department of Cancer Medicine, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France (L.A.); Bradford Hill Clinical Research Center, Santiago (M.B.), and James Lind Centro de Investigación del Cáncer, Temuco (E.Y.R.) - both in Chile; the Postgraduate Medical Center, Department of Oncology, European Health Center, Otwock, Warsaw (C. Szczylik), and the Department of Outpatient Chemotherapy, Professor Franciszek Łukaszczyk Oncology Center, Bydgoszcz (B.Z.) - both in Poland; Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IRCCS, Padua, Italy (M.M.); Consultorio de Medicina Especializada, Benito Juárez, Mexico City (A.S.Z.); Instituto de Oncología de Rosario, Rosario, Argentina (L.E.F.); Latin American Cooperative Oncology Group, Porto Alegre, and Beneficência Portuguesa de São Paulo, São Paulo - both in Brazil (F.A.S.); the Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada (D.Y.C.H.); Exelixis, Alameda, CA (F.W., F.M., Y.-L.C.); Bristol Myers Squibb, Boudry, Switzerland (M.K.L.); the Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona (C. Suarez); and the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.J.M.).
Fabio A SchutzFrom the Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School - both in Boston (T.K.C.); the Department of Genitourinary Oncology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free NHS Trust, London (T.P.); the Department of Cancer Medicine, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France (L.A.); Bradford Hill Clinical Research Center, Santiago (M.B.), and James Lind Centro de Investigación del Cáncer, Temuco (E.Y.R.) - both in Chile; the Postgraduate Medical Center, Department of Oncology, European Health Center, Otwock, Warsaw (C. Szczylik), and the Department of Outpatient Chemotherapy, Professor Franciszek Łukaszczyk Oncology Center, Bydgoszcz (B.Z.) - both in Poland; Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IRCCS, Padua, Italy (M.M.); Consultorio de Medicina Especializada, Benito Juárez, Mexico City (A.S.Z.); Instituto de Oncología de Rosario, Rosario, Argentina (L.E.F.); Latin American Cooperative Oncology Group, Porto Alegre, and Beneficência Portuguesa de São Paulo, São Paulo - both in Brazil (F.A.S.); the Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada (D.Y.C.H.); Exelixis, Alameda, CA (F.W., F.M., Y.-L.C.); Bristol Myers Squibb, Boudry, Switzerland (M.K.L.); the Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona (C. Suarez); and the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.J.M.).
Daniel Y C HengFrom the Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School - both in Boston (T.K.C.); the Department of Genitourinary Oncology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free NHS Trust, London (T.P.); the Department of Cancer Medicine, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France (L.A.); Bradford Hill Clinical Research Center, Santiago (M.B.), and James Lind Centro de Investigación del Cáncer, Temuco (E.Y.R.) - both in Chile; the Postgraduate Medical Center, Department of Oncology, European Health Center, Otwock, Warsaw (C. Szczylik), and the Department of Outpatient Chemotherapy, Professor Franciszek Łukaszczyk Oncology Center, Bydgoszcz (B.Z.) - both in Poland; Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IRCCS, Padua, Italy (M.M.); Consultorio de Medicina Especializada, Benito Juárez, Mexico City (A.S.Z.); Instituto de Oncología de Rosario, Rosario, Argentina (L.E.F.); Latin American Cooperative Oncology Group, Porto Alegre, and Beneficência Portuguesa de São Paulo, São Paulo - both in Brazil (F.A.S.); the Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada (D.Y.C.H.); Exelixis, Alameda, CA (F.W., F.M., Y.-L.C.); Bristol Myers Squibb, Boudry, Switzerland (M.K.L.); the Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona (C. Suarez); and the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.J.M.).
Fong WangFrom the Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School - both in Boston (T.K.C.); the Department of Genitourinary Oncology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free NHS Trust, London (T.P.); the Department of Cancer Medicine, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France (L.A.); Bradford Hill Clinical Research Center, Santiago (M.B.), and James Lind Centro de Investigación del Cáncer, Temuco (E.Y.R.) - both in Chile; the Postgraduate Medical Center, Department of Oncology, European Health Center, Otwock, Warsaw (C. Szczylik), and the Department of Outpatient Chemotherapy, Professor Franciszek Łukaszczyk Oncology Center, Bydgoszcz (B.Z.) - both in Poland; Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IRCCS, Padua, Italy (M.M.); Consultorio de Medicina Especializada, Benito Juárez, Mexico City (A.S.Z.); Instituto de Oncología de Rosario, Rosario, Argentina (L.E.F.); Latin American Cooperative Oncology Group, Porto Alegre, and Beneficência Portuguesa de São Paulo, São Paulo - both in Brazil (F.A.S.); the Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada (D.Y.C.H.); Exelixis, Alameda, CA (F.W., F.M., Y.-L.C.); Bristol Myers Squibb, Boudry, Switzerland (M.K.L.); the Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona (C. Suarez); and the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.J.M.).
Fabio MataveliFrom the Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School - both in Boston (T.K.C.); the Department of Genitourinary Oncology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free NHS Trust, London (T.P.); the Department of Cancer Medicine, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France (L.A.); Bradford Hill Clinical Research Center, Santiago (M.B.), and James Lind Centro de Investigación del Cáncer, Temuco (E.Y.R.) - both in Chile; the Postgraduate Medical Center, Department of Oncology, European Health Center, Otwock, Warsaw (C. Szczylik), and the Department of Outpatient Chemotherapy, Professor Franciszek Łukaszczyk Oncology Center, Bydgoszcz (B.Z.) - both in Poland; Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IRCCS, Padua, Italy (M.M.); Consultorio de Medicina Especializada, Benito Juárez, Mexico City (A.S.Z.); Instituto de Oncología de Rosario, Rosario, Argentina (L.E.F.); Latin American Cooperative Oncology Group, Porto Alegre, and Beneficência Portuguesa de São Paulo, São Paulo - both in Brazil (F.A.S.); the Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada (D.Y.C.H.); Exelixis, Alameda, CA (F.W., F.M., Y.-L.C.); Bristol Myers Squibb, Boudry, Switzerland (M.K.L.); the Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona (C. Suarez); and the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.J.M.).
Yu-Lin ChangFrom the Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School - both in Boston (T.K.C.); the Department of Genitourinary Oncology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free NHS Trust, London (T.P.); the Department of Cancer Medicine, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France (L.A.); Bradford Hill Clinical Research Center, Santiago (M.B.), and James Lind Centro de Investigación del Cáncer, Temuco (E.Y.R.) - both in Chile; the Postgraduate Medical Center, Department of Oncology, European Health Center, Otwock, Warsaw (C. Szczylik), and the Department of Outpatient Chemotherapy, Professor Franciszek Łukaszczyk Oncology Center, Bydgoszcz (B.Z.) - both in Poland; Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IRCCS, Padua, Italy (M.M.); Consultorio de Medicina Especializada, Benito Juárez, Mexico City (A.S.Z.); Instituto de Oncología de Rosario, Rosario, Argentina (L.E.F.); Latin American Cooperative Oncology Group, Porto Alegre, and Beneficência Portuguesa de São Paulo, São Paulo - both in Brazil (F.A.S.); the Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada (D.Y.C.H.); Exelixis, Alameda, CA (F.W., F.M., Y.-L.C.); Bristol Myers Squibb, Boudry, Switzerland (M.K.L.); the Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona (C. Suarez); and the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.J.M.).
Maximiliano van Kooten LosioFrom the Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School - both in Boston (T.K.C.); the Department of Genitourinary Oncology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free NHS Trust, London (T.P.); the Department of Cancer Medicine, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France (L.A.); Bradford Hill Clinical Research Center, Santiago (M.B.), and James Lind Centro de Investigación del Cáncer, Temuco (E.Y.R.) - both in Chile; the Postgraduate Medical Center, Department of Oncology, European Health Center, Otwock, Warsaw (C. Szczylik), and the Department of Outpatient Chemotherapy, Professor Franciszek Łukaszczyk Oncology Center, Bydgoszcz (B.Z.) - both in Poland; Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IRCCS, Padua, Italy (M.M.); Consultorio de Medicina Especializada, Benito Juárez, Mexico City (A.S.Z.); Instituto de Oncología de Rosario, Rosario, Argentina (L.E.F.); Latin American Cooperative Oncology Group, Porto Alegre, and Beneficência Portuguesa de São Paulo, São Paulo - both in Brazil (F.A.S.); the Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada (D.Y.C.H.); Exelixis, Alameda, CA (F.W., F.M., Y.-L.C.); Bristol Myers Squibb, Boudry, Switzerland (M.K.L.); the Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona (C. Suarez); and the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.J.M.).
Cristina SuarezFrom the Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School - both in Boston (T.K.C.); the Department of Genitourinary Oncology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free NHS Trust, London (T.P.); the Department of Cancer Medicine, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France (L.A.); Bradford Hill Clinical Research Center, Santiago (M.B.), and James Lind Centro de Investigación del Cáncer, Temuco (E.Y.R.) - both in Chile; the Postgraduate Medical Center, Department of Oncology, European Health Center, Otwock, Warsaw (C. Szczylik), and the Department of Outpatient Chemotherapy, Professor Franciszek Łukaszczyk Oncology Center, Bydgoszcz (B.Z.) - both in Poland; Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IRCCS, Padua, Italy (M.M.); Consultorio de Medicina Especializada, Benito Juárez, Mexico City (A.S.Z.); Instituto de Oncología de Rosario, Rosario, Argentina (L.E.F.); Latin American Cooperative Oncology Group, Porto Alegre, and Beneficência Portuguesa de São Paulo, São Paulo - both in Brazil (F.A.S.); the Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada (D.Y.C.H.); Exelixis, Alameda, CA (F.W., F.M., Y.-L.C.); Bristol Myers Squibb, Boudry, Switzerland (M.K.L.); the Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona (C. Suarez); and the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.J.M.).
Robert J MotzerFrom the Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School - both in Boston (T.K.C.); the Department of Genitourinary Oncology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free NHS Trust, London (T.P.); the Department of Cancer Medicine, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France (L.A.); Bradford Hill Clinical Research Center, Santiago (M.B.), and James Lind Centro de Investigación del Cáncer, Temuco (E.Y.R.) - both in Chile; the Postgraduate Medical Center, Department of Oncology, European Health Center, Otwock, Warsaw (C. Szczylik), and the Department of Outpatient Chemotherapy, Professor Franciszek Łukaszczyk Oncology Center, Bydgoszcz (B.Z.) - both in Poland; Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto IRCCS, Padua, Italy (M.M.); Consultorio de Medicina Especializada, Benito Juárez, Mexico City (A.S.Z.); Instituto de Oncología de Rosario, Rosario, Argentina (L.E.F.); Latin American Cooperative Oncology Group, Porto Alegre, and Beneficência Portuguesa de São Paulo, São Paulo - both in Brazil (F.A.S.); the Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada (D.Y.C.H.); Exelixis, Alameda, CA (F.W., F.M., Y.-L.C.); Bristol Myers Squibb, Boudry, Switzerland (M.K.L.); the Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona (C. Suarez); and the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (R.J.M.).
COSMIC-313 Investigators
Université Paris-Saclay · FRExelixis (United States) · USBrigham and Women's Hospital · USHebron University · PSMemorial Sloan Kettering Cancer Center · USQueen Mary University of London · GBUniversity of Calgary · CA

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI JENNIFER W MACK · 1985 to 2026
$330.6M
Treating the P13-Kinase/AKTP50CA101942 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI David McDermott · 2003 to 2026
$53.4M
Tissue-based biomarkers of anti-PD-1-based therapy in metastatic renal cell carcinomaR01CA266424 · NCI · DANA-FARBER CANCER INST · PI Toni Choueiri, SABINA SIGNORETTI · 2022 to 2026
$3.6M
NCI NIH HHS P30 CA006516NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA101942NCI NIH HHS R01 CA266424
6 · The paper itself

Abstract

backgroundThe efficacy and safety of treatment with cabozantinib in combination with nivolumab and ipilimumab in patients with previously untreated advanced renal-cell carcinoma are unknown.

methodsIn this phase 3, double-blind trial, we enrolled patients with advanced clear-cell renal-cell carcinoma who had not previously received treatment and had intermediate or poor prognostic risk according to the International Metastatic Renal-Cell Carcinoma Database Consortium categories. Patients were randomly assigned to receive 40 mg of cabozantinib daily in addition to nivolumab and ipilimumab (experimental group) or matched placebo in addition to nivolumab and ipilimumab (control group). Nivolumab (3 mg per kilogram of body weight) and ipilimumab (1 mg per kilogram) were administered once every 3 weeks for four cycles. Patients then received nivolumab maintenance therapy (480 mg once every 4 weeks) for up to 2 years. The primary end point was progression-free survival, as determined by blinded independent review according to Response Evaluation Criteria in Solid Tumors, version 1.1, and was assessed in the first 550 patients who had undergone randomization. The secondary end point was overall survival, assessed in all patients who had undergone randomization.

resultsOverall, 855 patients underwent randomization: 428 were assigned to the experimental group and 427 to the control group. Among the first 550 patients who had undergone randomization (276 in the experimental group and 274 in the control group), the probability of progression-free survival at 12 months was 0.57 in the experimental group and 0.49 in the control group (hazard ratio for disease progression or death, 0.73; 95% confidence interval, 0.57 to 0.94; P = 0.01); 43% of the patients in the experimental group and 36% in the control group had a response. Grade 3 or 4 adverse events occurred in 79% of the patients in the experimental group and in 56% in the control group. Follow-up for overall survival is ongoing.

conclusionsAmong patients with previously untreated, advanced renal-cell carcinoma who had intermediate or poor prognostic risk, treatment with cabozantinib plus nivolumab and ipilimumab resulted in significantly longer progression-free survival than treatment with nivolumab and ipilimumab alone. Grade 3 or 4 adverse events were more common in the experimental group than in the control group. (Funded by Exelixis; COSMIC-313 ClinicalTrials.gov number, NCT03937219.).

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsCarcinoma, Renal CellKidney NeoplasmsAnilidesDouble-Blind MethodHumansIpilimumabNivolumabPrognosisPyridinesSurvival AnalysisAnilidescabozantinibIpilimumabNivolumabPyridines

Identifiers

PMID37163623
PMCPMC10257898
OpenAlexW4376107652

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