CoChat
Sign Up
Cited by 3,063Cancer Immunotherapy and BiomarkersLung Cancer Treatments and MutationsLung Cancer Diagnosis and Treatment

The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.

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

Open access
Hellmann, Matthew D., Ciuleanu, Tudor-Eliade, Pluzanski, Adam, Lee, Jong Seok, Otterson, Gregory A., Audigier-Valette, Clarisse, Minenza, Elisa, Linardou, Helena, Burgers, Sjaak, Salman, Pamela, Borghaei, Hossein, Ramalingam, Suresh S., Brahmer, Julie, Reck, Martin, O’Byrne, Kenneth J., Geese, William J., Green, George, Chang, Han, Szustakowski, Joseph, Bhagavatheeswaran, Prabhu, Healey, Diane, Fu, Yali, Nathan, Faith, Paz-Ares, Luis·2018·New England Journal of Medicine
DOI 10.1056/nejmoa1801946PMC PMC7193684
Open this paper in CoChat — free accountOpen PDF

Abstract

BACKGROUND: Nivolumab 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). METHODS: We 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. RESULTS: Progression-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 .). CONCLUSIONS: Progression-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

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1056/nejmoa1801946

Cites

22 of 22 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Show all 22 references

Cited by

Sorted by citations

Items 1,001–1,002 of 1,002

Related

See all

Metadata

Authors
Hellmann, M. D., Ciuleanu, T.-E., Pluzanski, A., Lee, J. S., Otterson, G. A., Audigier-Valette, C., Minenza, E., Linardou, H., Burgers, S., Salman, P., Borghaei, H., Ramalingam, S. S., Brahmer, J., Reck, M., O’Byrne, K. J., Geese, W. J., Green, G., Chang, H., Szustakowski, J., Bhagavatheeswaran, P., Healey, D., Fu, Y., Nathan, F., & Paz-Ares, L.
Affiliations
  • Memorial Sloan Kettering Cancer Center (US)
  • From 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,...
  • Fox Chase Cancer Center (US)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2018-05-31
Volume
378
Issue
22
Pages
2093-2104
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa1801946
PMC
PMC7193684
OpenAlex
W2797675588
Cited by
3,063
References
22
Citations by year
2026: 100 · 2025: 184 · 2024: 222 · 2023: 289 · 2022: 419 · 2021: 499 · 2020: 559 · 2019: 542 · 2018: 247
FWCI
174.31
Type
journal article
Language
en
Open access
Licence
www.nejmgroup.org/legal/terms-of-use.htm (vor)
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
Bristol-Myers Squibb, Inc.
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
Keywords
nivolumab, ipilimumab, non-small cell lung cancer, tumor mutational burden, PD-L1 expression, immune checkpoint inhibitors, progression-free survival, chemotherapy comparison, stage IV lung cancer, treatment-related adverse events, treatment response biomarkers, objective response rate, immunotherapy biomarkers, safety and tolerability
MeSH terms
Antineoplastic Agents, Immunological, Ipilimumab, Nivolumab, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Neoplasm Staging, Biomarkers, Tumor, Disease-Free Survival, Kaplan-Meier Estimate, B7-H1 Antigen

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review