The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
Pembrolizumab versus Ipilimumab in Advanced Melanoma
Open accessAbstract
BACKGROUND: The immune checkpoint inhibitor ipilimumab is the standard-of-care treatment for patients with advanced melanoma. Pembrolizumab inhibits the programmed cell death 1 (PD-1) immune checkpoint and has antitumor activity in patients with advanced melanoma. METHODS: In this randomized, controlled, phase 3 study, we assigned 834 patients with advanced melanoma in a 1:1:1 ratio to receive pembrolizumab (at a dose of 10 mg per kilogram of body weight) every 2 weeks or every 3 weeks or four doses of ipilimumab (at 3 mg per kilogram) every 3 weeks. Primary end points were progression-free and overall survival. RESULTS: The estimated 6-month progression-free-survival rates were 47.3% for pembrolizumab every 2 weeks, 46.4% for pembrolizumab every 3 weeks, and 26.5% for ipilimumab (hazard ratio for disease progression, 0.58; P<0.001 for both pembrolizumab regimens versus ipilimumab; 95% confidence intervals [CIs], 0.46 to 0.72 and 0.47 to 0.72, respectively). Estimated 12-month survival rates were 74.1%, 68.4%, and 58.2%, respectively (hazard ratio for death for pembrolizumab every 2 weeks, 0.63; 95% CI, 0.47 to 0.83; P=0.0005; hazard ratio for pembrolizumab every 3 weeks, 0.69; 95% CI, 0.52 to 0.90; P=0.0036). The response rate was improved with pembrolizumab administered every 2 weeks (33.7%) and every 3 weeks (32.9%), as compared with ipilimumab (11.9%) (P<0.001 for both comparisons). Responses were ongoing in 89.4%, 96.7%, and 87.9% of patients, respectively, after a median follow-up of 7.9 months. Efficacy was similar in the two pembrolizumab groups. Rates of treatment-related adverse events of grade 3 to 5 severity were lower in the pembrolizumab groups (13.3% and 10.1%) than in the ipilimumab group (19.9%). CONCLUSIONS: The anti-PD-1 antibody pembrolizumab prolonged progression-free survival and overall survival and had less high-grade toxicity than did ipilimumab in patients with advanced melanoma. (Funded by Merck Sharp & Dohme; KEYNOTE-006 ClinicalTrials.gov number, NCT01866319.).
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.
Integrity signals
Registry
Cites
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.
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?
The cited source doesn’t support the claim as written.
In the citing paper
“however responses to these therapies are often heterogeneous and not durable (1–3).”
From Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients (2018) · cites this paper as [2]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Immune checkpoint blockade with monoclonal antibodies (mAbs) targeting programmed cell death protein 1 (PD-1) provides long-term clinical benefits to nearly 40% of patients with advanced melanoma (1–5).”
From Fecal microbiota transplant overcomes resistance to anti–PD-1 therapy in melanoma patients (2021) · cites this paper as [5]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Clinical trials of ICPis excluded patients with pre-existing active autoimmune diseases because of concerns of a high susceptibility to severe irAEs [49,50].”
From Graves’ Disease during Immune Checkpoint Inhibitor Therapy (A Case Series and Literature Review) (2021) · cites this paper as [50]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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 [3]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“There were 16 responders (from here on, referred to as R) and 26 nonresponders (NR), yielding a response rate of 38%, which is in line with published clinical data of anti–PD-1 therapy in metastatic melanoma patients (5, 6).”
From The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients (2018) · cites this paper as [6]
In the citing paper
“Severe adverse reactions include severe diarrhea, colitis, increased alanine aminotransferase levels, inflammation pneumonitis, and interstitial nephritis (67, 73, 99).”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [73]
In the citing paper
“In the subsequent phase III clinical trial, more than 30% of patients with advanced melanoma achieved an objective response following pembrolizumab monotherapy compared with 12% of patients treated with ipilimumab alone (58).”
From Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance (2021) · cites this paper as [58]
In the citing paper
“Response rates range from 15 to 30% (in most solid tumors) to 45–60% (in melanoma and MSI-H tumors).”
From Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors (2019) · cites this paper as [2]
In the citing paper
“In order to limit the risk of severe immune-related adverse events (irAEs) or exacerbation of underlying autoimmune or inflammatory disease, patients with preexisting autoimmune disorders (ADs) or those receiving systemic immunosuppression for organ transplantation have been universally excluded from clinical trials.3,4”
From Autoimmune diseases and immune-checkpoint inhibitors for cancer therapy: Review of the literature and personalized risk-based prevention strategy (2020) · cites this paper as [4]
In the citing paper
“At present, antibodies blocking PD-1 or its ligand PD-L1 have been approved to treat various solid and hematologic malignancies (Table 1) [7–12].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [11]
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
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)
Eisenhauer, E. A., Therasse, P., Bogaerts, J., Schwartz, L. H., Sargent, D., Ford, R., Dancey, J., Arbuck, S., Gwyther, S., Mooney, M., et al. (2009) · European Journal of Cancer · doi:10.1016/j.ejca.2008.10.026 · Cited by 29,534
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1003466 · Cited by 15,155
Self-citationThe blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838
Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer
Rizvi, N. A., Hellmann, M. D., Snyder, A., Kvistborg, P., Makarov, V., Havel, J. J., Lee, W., Yuan, J., Wong, P., Ho, T. S., et al. (2015) · Science · doi:10.1126/science.aaa1348 · Cited by 7,802
Improved survival with vemurafenib in melanoma with BRAF V600E mutation
Chapman, P. B., Hauschild, A., Robert, C., Haanen, J. B., Ascierto, P., Larkin, J., Dummer, R., Garbe, C., Testori, A., Maio, M., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1103782 · Cited by 7,720
Self-citationPD-1 blockade induces responses by inhibiting adaptive immune resistance
Tumeh, P. C., Harview, C. L., Yearley, J. H., Shintaku, I. P., Taylor, E. J. M., Robert, L., Chmielowski, B., Spasic, M., Henry, G., Ciobanu, V., et al. (2014) · Nature · doi:10.1038/nature13954 · Cited by 6,609
Self-citationNivolumab in Previously Untreated Melanoma without BRAF Mutation
Robert, C., Long, G. V., Brady, B., Dutriaux, C., Maio, M., Mortier, L., Hassel, J. C., Rutkowski, P., McNeil, C., Kalinka-Warzocha, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1412082 · Cited by 5,519
Self-citationIpilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma
Robert, C., Thomas, L., Bondarenko, I., O'Day, S., Weber, J., Garbe, C., Lebbe, C., Baurain, J.-F., Testori, A., Grob, J.-J., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1104621 · Cited by 4,496
Self-citationNivolumab plus Ipilimumab in Advanced Melanoma
Wolchok, J. D., Kluger, H., Callahan, M. K., Postow, M. A., Rizvi, N. A., Lesokhin, A. M., Segal, N. H., Ariyan, C. E., Gordon, R.-A., Reed, K., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1302369 · Cited by 4,230
Enhancement of Antitumor Immunity by CTLA-4 Blockade
Leach, D. R., Krummel, M. F., & Allison, J. P. (1996) · Science · doi:10.1126/science.271.5256.1734 · Cited by 3,955
Research works printed but not linked: 2
- Ribas A, 2014, Pigment Cell Melanoma Res, 27, 1223
- Robert C, 2014, Ann Oncol, 25, LBA34
Cited by
Sorted by citations
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer
Reck, M., Rodríguez-Abreu, D., Robinson, A. G., Hui, R., Csőszi, T., Fülöp, A., Gottfried, M., Peled, N., Tafreshi, A., Cuffe, S., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1606774 · Cited by 10,089
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma
Larkin, J., Chiarion-Sileni, V., Gonzalez, R., Grob, J. J., Cowey, C. L., Lao, C. D., Schadendorf, D., Dummer, R., Smylie, M., Rutkowski, P., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504030 · Cited by 8,157
Self-citationCancer immunotherapy using checkpoint blockade
Ribas, A., & Wolchok, J. D. (2018) · Science · doi:10.1126/science.aar4060 · Cited by 6,791
Self-citationCancer treatment and survivorship statistics, 2016
Miller, K. D., Siegel, R. L., Lin, C. C., Mariotto, A. B., Kramer, J. L., Rowland, J. H., Stein, K. D., Alteri, R., & Jemal, A. (2016) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21349 · Cited by 6,066
Metadata
- Authors
- Robert, C., Schachter, J., Long, G. V., Arance, A., Grob, J. J., Mortier, L., Daud, A., Carlino, M. S., McNeil, C., Lotem, M., Larkin, J., Lorigan, P., Neyns, B., Blank, C. U., Hamid, O., Mateus, C., Shapira-Frommer, R., Kosh, M., Zhou, H., Ibrahim, N., Ebbinghaus, S., & Ribas, A.
- Affiliations
- Université Paris-Sud (FR)
- Sheba Medical Center (IL)
- Hospital Clínic de Barcelona (ES)
- Hôpital de la Timone (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- University of California, San Francisco (US)
- Royal Prince Alfred Hospital (AU)
- Hadassah Medical Center (IL)
- Royal Marsden Hospital (GB)
- University of Manchester (GB)
- Universitair Ziekenhuis Brussel (BE)
- The Netherlands Cancer Institute (NL)
- Angeles Clinic and Research Institute (US)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- University of California, Los Angeles (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2015-06-25
- Volume
- 372
- Issue
- 26
- Pages
- 2521-2532
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2152897456
- Semantic Scholar
- 0dac3ea80083f0a86598cb9af0a205554280551b
- Cited by
- 5,887
- References
- 26
- Citations by year
- 2026: 234 · 2025: 298 · 2024: 374 · 2023: 421 · 2022: 471 · 2021: 568 · 2020: 659 · 2019: 585 · 2018: 684 · 2017: 761 · 2016: 628 · 2015: 188
- FWCI
- 329.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion, other-oa)
- Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- Amgen
- Bristol-Myers Squibb
- Pfizer
- GlaxoSmithKline
- Genentech
- Kite Pharma
- 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
- ipilimumab, advanced melanoma, immune checkpoint inhibitors, anti-PD-1 therapy, CTLA-4 inhibition, progression-free survival, overall survival, dosing frequency, treatment-related adverse events, immune-related adverse events, response rate
- MeSH terms
- Ipilimumab, Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antineoplastic Agents, Female, Humans, Male, Melanoma, Middle Aged, Skin Neoplasms, Survival Analysis, Young Adult, Programmed Cell Death 1 Receptor, Antibodies, Monoclonal, Humanized
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
