Evidence map›Paper›PMID 29658845›Full record

Trial reportThe New England journal of medicine2018

Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden.

Matthew D Hellmann, Tudor-Eliade Ciuleanu, Adam Pluzanski, Jong Seok Lee, Gregory A Otterson, Clarisse Audigier-Valette, Elisa Minenza, Helena Linardou, Sjaak Burgers, Pamela Salman and 14 more

4 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
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 4 registered trials, which are not on this map. Cited by 1,806 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1,806citing papers in PubMed, 7 pooled it
181.1field-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.

NCT02477826 phase3completednot on this map

An Open-Label, Randomized Phase 3 Trial of Nivolumab, or Nivolumab Plus Ipilimumab, or Nivolumab Plus Platinum Doublet Chemotherapy Versus Platinum Doublet Chemotherapy in Subjects With Chemotherapy-Naïve Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC)

TypeinterventionalSponsorBristol-Myers SquibbRan2015 to 2024Enrolled2,747ConditionsNon-Small Cell Lung CancerArmsNivolumab, Ipilimumab, Carboplatin, Cisplatin, Gemcitabine
NCT03918252 phase2active not recruitingnot on this mapstarted 2019, after this paper: background citation

Neoadjuvant Immune Checkpoint Blockade in Resectable Malignant Pleural Mesothelioma

TypeinterventionalSponsorSidney Kimmel Comprehensive Cancer Center at Johns HopkinsRan2019 to 2028Enrolled30ConditionsMesotheliomaArmsNivolumab Injection, Ipilimumab Injection
NCT04141644 phase1active not recruitingnot on this mapstarted 2020, after this paper: background citation

A Phase Ib Study to Evaluate the Safety and Efficacy of Osimertinib in Combination With Ipilimumab in Patients With EGFR Mutated Non-Small-Cell Lung Cancer Tumors

TypeinterventionalSponsorUniversity of UtahRan2020 to 2028Enrolled24ConditionsNon-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor (Disorder)ArmsIpilimumab, Osimertinib
NCT05378334 narecruitingnot on this mapstarted 2022, after this paper: background citation

Efficacy and Safety of Bone-protecting and Mass-dispersesing Decoction (HuGuXiaoJiTang, HGXJT) Combining With ICIs in Bone Metastatic NSCLC Patients

TypeinterventionalSponsorGuangzhou University of Traditional Chinese MedicineRan2022 to 2028Enrolled82ConditionsNon-small Cell Lung CancerArmsICI, Chemotherapy, Placebo, Bone-protecting and Mass-dispersesing Decoction
3 · Its place in the literature

Who cites it

1,806 citing papers in PubMed, 7 syntheses or guidelines pooled it, 3,112 citations in OpenAlex.

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  8. TAPISTRY: A Phase II Study of Atezolizumab in Patients with Tumor Mutational Burden-High Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
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  18. Towards liquid biopsy-based analysis of antitumour immunity.Nature reviews. Clinical oncology · 2026
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1,746 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 12 institutions in 13 countries.

Matthew D HellmannFrom Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hôpital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundación Arturo López Pérez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.).ORCID 0000-0002-2670-9777
Tudor-Eliade CiuleanuFrom Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hôpital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundación Arturo López Pérez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.).
Adam PluzanskiFrom Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hôpital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundación Arturo López Pérez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.).
Jong Seok LeeFrom Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hôpital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundación Arturo López Pérez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.).
Gregory A OttersonFrom Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hôpital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundación Arturo López Pérez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.).
Clarisse Audigier-ValetteFrom Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hôpital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundación Arturo López Pérez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.).
Elisa MinenzaFrom Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hôpital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundación Arturo López Pérez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.).
Helena LinardouFrom Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hôpital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundación Arturo López Pérez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.).
Sjaak BurgersFrom Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hôpital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundación Arturo López Pérez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.).
Pamela SalmanFrom Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hôpital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundación Arturo López Pérez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.).
Hossein BorghaeiFrom Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hôpital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundación Arturo López Pérez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.).
Suresh S RamalingamFrom Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hôpital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundación Arturo López Pérez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.).
Julie BrahmerFrom Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hôpital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundación Arturo López Pérez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.).
Martin ReckFrom Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hôpital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundación Arturo López Pérez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.).
Kenneth J O'ByrneFrom Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hôpital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundación Arturo López Pérez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.).
William J GeeseFrom Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hôpital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundación Arturo López Pérez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.).
George GreenFrom Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hôpital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundación Arturo López Pérez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.).
Han ChangFrom Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hôpital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundación Arturo López Pérez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.).
Joseph SzustakowskiFrom Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hôpital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundación Arturo López Pérez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.).
Prabhu BhagavatheeswaranFrom Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hôpital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundación Arturo López Pérez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.).
Diane HealeyFrom Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hôpital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundación Arturo López Pérez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.).
Yali FuFrom Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hôpital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundación Arturo López Pérez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.).
Faith NathanFrom Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hôpital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundación Arturo López Pérez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.).
Luis Paz-AresFrom Memorial Sloan Kettering Cancer Center Hospital, New York (M.D.H.); Prof. Dr. Ion Chiricuta Institute of Oncology and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland (A.P.); Seoul National University Bundang Hospital, Seoul, South Korea (J.S.L.); Ohio State University, Columbus (G.A.O.); Hôpital Sainte Musse, Toulon, France (C.A.-V.); Ospedale Santa Maria della Misericordia, Perugia, Italy (E.M.); First Department of Oncology, Metropolitan Hospital, Athens, Greece (H.L.); Antoni van Leeuwenhoek Ziekenhuis, Amsterdam (S.B.); Fundación Arturo López Pérez, Santiago, Chile (P.S.); Fox Chase Cancer Center, Philadelphia (H.B.); Winship Cancer Institute, Emory University, Atlanta (S.S.R.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.B.); LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany (M.R.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., G.G., H.C., J.S., P.B., D.H., Y.F., F.N.); and Hospital Universitario 12 de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and CiberOnc, Madrid (L.P.-A.).
Bristol-Myers Squibb (United States) · USCentrum Onkologii · PLEmory University · USFox Chase Cancer Center · USGerman Center for Lung Research · DEHospital Universitario 12 De Octubre · ESIuliu Hațieganu University of Medicine and Pharmacy · ROMemorial Sloan Kettering Cancer Center · USOspedale Santa Maria · ITPrincess Alexandra Hospital · AUSeoul National University Bundang Hospital · KRThe Netherlands Cancer Institute · NL

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Jennifer A. Woyach · 1985 to 2026
$132.3M
NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA016058
6 · The paper itself

Abstract

backgroundNivolumab plus ipilimumab showed promising efficacy for the treatment of non-small-cell lung cancer (NSCLC) in a phase 1 trial, and tumor mutational burden has emerged as a potential biomarker of benefit. In this part of an open-label, multipart, phase 3 trial, we examined progression-free survival with nivolumab plus ipilimumab versus chemotherapy among patients with a high tumor mutational burden (≥10 mutations per megabase).

methodsWe enrolled patients with stage IV or recurrent NSCLC that was not previously treated with chemotherapy. Those with a level of tumor programmed death ligand 1 (PD-L1) expression of at least 1% were randomly assigned, in a 1:1:1 ratio, to receive nivolumab plus ipilimumab, nivolumab monotherapy, or chemotherapy; those with a tumor PD-L1 expression level of less than 1% were randomly assigned, in a 1:1:1 ratio, to receive nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy. Tumor mutational burden was determined by the FoundationOne CDx assay.

resultsProgression-free survival among patients with a high tumor mutational burden was significantly longer with nivolumab plus ipilimumab than with chemotherapy. The 1-year progression-free survival rate was 42.6% with nivolumab plus ipilimumab versus 13.2% with chemotherapy, and the median progression-free survival was 7.2 months (95% confidence interval [CI], 5.5 to 13.2) versus 5.5 months (95% CI, 4.4 to 5.8) (hazard ratio for disease progression or death, 0.58; 97.5% CI, 0.41 to 0.81; P<0.001). The objective response rate was 45.3% with nivolumab plus ipilimumab and 26.9% with chemotherapy. The benefit of nivolumab plus ipilimumab over chemotherapy was broadly consistent within subgroups, including patients with a PD-L1 expression level of at least 1% and those with a level of less than 1%. The rate of grade 3 or 4 treatment-related adverse events was 31.2% with nivolumab plus ipilimumab and 36.1% with chemotherapy. ical; CheckMate 227 ClinicalTrials.gov number, NCT02477826 .).

conclusionsProgression-free survival was significantly longer with first-line nivolumab plus ipilimumab than with chemotherapy among patients with NSCLC and a high tumor mutational burden, irrespective of PD-L1 expression level. The results validate the benefit of nivolumab plus ipilimumab in NSCLC and the role of tumor mutational burden as a biomarker for patient selection. (Funded by Bristol-Myers Squibb and Ono Pharmaceut

Indexed as

MutationAdultAgedAged, 80 and overAntibodies, MonoclonalAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungDisease-Free SurvivalFemaleHumansIpilimumabKaplan-Meier EstimateLung NeoplasmsAntibodies, MonoclonalAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorCD274 protein, humanIpilimumabNivolumab

Identifiers

PMID29658845
PMCPMC7193684
OpenAlexW2797675588

What OpenQuestion holds

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Registered trials

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.