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Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma
Open accessAbstract
BACKGROUND: Nivolumab combined with ipilimumab resulted in longer progression-free survival and a higher objective response rate than ipilimumab alone in a phase 3 trial involving patients with advanced melanoma. We now report 3-year overall survival outcomes in this trial. METHODS: We randomly assigned, in a 1:1:1 ratio, patients with previously untreated advanced melanoma to receive nivolumab at a dose of 1 mg per kilogram of body weight plus ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses, followed by nivolumab at a dose of 3 mg per kilogram every 2 weeks; nivolumab at a dose of 3 mg per kilogram every 2 weeks plus placebo; or ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses plus placebo, until progression, the occurrence of unacceptable toxic effects, or withdrawal of consent. Randomization was stratified according to programmed death ligand 1 (PD-L1) status, BRAF mutation status, and metastasis stage. The two primary end points were progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group versus the ipilimumab group. RESULTS: At a minimum follow-up of 36 months, the median overall survival had not been reached in the nivolumab-plus-ipilimumab group and was 37.6 months in the nivolumab group, as compared with 19.9 months in the ipilimumab group (hazard ratio for death with nivolumab plus ipilimumab vs. ipilimumab, 0.55 [P<0.001]; hazard ratio for death with nivolumab vs. ipilimumab, 0.65 [P<0.001]). The overall survival rate at 3 years was 58% in the nivolumab-plus-ipilimumab group and 52% in the nivolumab group, as compared with 34% in the ipilimumab group. The safety profile was unchanged from the initial report. Treatment-related adverse events of grade 3 or 4 occurred in 59% of the patients in the nivolumab-plus-ipilimumab group, in 21% of those in the nivolumab group, and in 28% of those in the ipilimumab group. CONCLUSIONS: Among patients with advanced melanoma, significantly longer overall survival occurred with combination therapy with nivolumab plus ipilimumab or with nivolumab alone than with ipilimumab alone. (Funded by Bristol-Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505 .).
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“with anti-PD-1 and anti-PD-1/CTLA-4 combination therapy emerging as most effective [3, 4].”
From Relating the gut metagenome and metatranscriptome to immunotherapy responses in melanoma patients (2019) · cites this paper as [4]
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“3-year overall survival rates were 58%, 52%, and 34% in combination therapy, anti-PD-1, and anti-CTLA-4 groups, respectively [4].”
From Relating the gut metagenome and metatranscriptome to immunotherapy responses in melanoma patients (2019) · cites this paper as [4]
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“These chemokines have been identified as the dominant mediators for the recruitment of CXCR3+ and CCR5+ tumor-specific T lymphocytes into the tumors and their intratumoral expression correlated with favorable clinical outcomes in patients with melanoma30–32.”
From Epigenetic state determines the in vivo efficacy of STING agonist therapy (2023) · cites this paper as [30]
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“Third, many of these studies utilized ICIs as monotherapy in a heavily pretreated population whereas current standard first-line therapy often includes a combination of ICIs or ICI with chemotherapy for multiple tumor types (35–40).”
From A Uniform Computational Approach Improved on Existing Pipelines to Reveal Microbiome Biomarkers of Nonresponse to Immune Checkpoint Inhibitors (2021) · cites this paper as [36]
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“By contrast, ICB has shown promise in the adjuvant setting in patients with melanoma or NSCLC57–59”
From Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges (2018) · cites this paper as [59]
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Metadata
- Authors
- Wolchok, J. D., Chiarion-Sileni, V., Gonzalez, R., Rutkowski, P., Grob, J.-J., Cowey, C. L., Lao, C. D., Wagstaff, J., Schadendorf, D., Ferrucci, P. F., Smylie, M., Dummer, R., Hill, A., Hogg, D., Haanen, J., Carlino, M. S., Bechter, O., Maio, M., Marquez-Rodas, I., Guidoboni, M., McArthur, G., Lebbé, C., Ascierto, P. A., Long, G. V., Cebon, J., Sosman, J., Postow, M. A., Callahan, M. K., Walker, D., Rollin, L., Bhore, R., Hodi, F. S., & Larkin, J.
- Affiliations
- University of Siena (IT)
- From the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W., M.A.P., M.K.C.); Oncology Institute of Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (V.C.-S.), European Institute of Oncology, Milan (P.F.F.), Center for Immuno-Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena (M.M.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.),...
- ORCID
- Wolchok, Jedd D.
- Gonzalez, Rene
- Rutkowski, Piotr
- Grob, Jean-Jacques
- Cowey, C. Lance
- Wagstaff, John
- Schadendorf, Dirk
- Ferrucci, Pier F.
- Smylie, Michael
- Dummer, Reinhard
- Hogg, David
- Haanen, John
- Carlino, Matteo S.
- Bechter, Oliver
- Maio, Michele
- Guidoboni, Massimo
- McArthur, Grant
- Ascierto, Paolo A.
- Long, Georgina V.
- Cebon, Jonathan
- Sosman, Jeffrey
- Postow, Michael A.
- Callahan, Margaret K.
- Bhore, Rafia
- Hodi, F. Stephen
- Larkin, James
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2017-10-05
- Volume
- 377
- Issue
- 14
- Pages
- 1345-1356
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC5706778
- OpenAlex
- W2753432434
- Semantic Scholar
- 23dbeed54cde655fb6a12697b02c9ff303515da7
- Cited by
- 5,357
- References
- 18
- Citations by year
- 2026: 159 · 2025: 282 · 2024: 569 · 2023: 705 · 2022: 746 · 2021: 947 · 2020: 900 · 2019: 578 · 2018: 428 · 2017: 37
- FWCI
- 234.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Use Siena air (University of Siena) (submittedVersion, other-oa)
- Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Lirias (submittedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Cancer Institute (P30CA008748)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- advanced melanoma, nivolumab, ipilimumab, combination immunotherapy, immune checkpoint inhibitors, PD-1 inhibitors, CTLA-4 inhibitors, overall survival, progression-free survival, treatment-related adverse events, immune-related adverse events, PD-L1 expression, BRAF mutation, long-term follow-up
- MeSH terms
- Ipilimumab, Nivolumab, Adult, Aged, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Double-Blind Method, Humans, Melanoma, Middle Aged, Neoplasm Staging, Skin Neoplasms, Survival Rate, Disease-Free Survival, Kaplan-Meier Estimate
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