The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
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 .).
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 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 [4]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“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]
Experimental — accuracy not yet measuredIn the citing paper
“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]
In the citing paper
“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]
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
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
Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,320
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 · cited 9×
“Asthenia 30 (10) 1 (<1) 25 (8) 1 (<1) 17 (5) 2 (1)”
InfluentialSelf-citationCombined 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-citationPembrolizumab versus Ipilimumab in Advanced Melanoma
Robert, C., Schachter, J., Long, G. V., Arance, A., Grob, J. J., Mortier, L., Daud, A., Carlino, M. S., McNeil, C., Lotem, M., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1503093 · Cited by 5,887 · cited 6×
“Asthenia 30 (10) 1 (<1) 25 (8) 1 (<1) 17 (5) 2 (1)”
InfluentialSelf-citationA sharper Bonferroni procedure for multiple tests of significance
HOCHBERG, Y. (1988) · Biometrika · doi:10.1093/biomet/75.4.800 · Cited by 4,829
(1997) · doi:10.1097/00005650-199711000-00002 · Cited by 4,544
Ipilimumab 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 · cited 9×
“Increased amylase level 26 (8) 9 (3) 20 (6) 6 (2) 15 (5) 4 (1)”
InfluentialSelf-citationTime‐Dependent ROC Curves for Censored Survival Data and a Diagnostic Marker
Heagerty, P. J., Lumley, T., & PEPE, M. S. (2000) · Biometrics · doi:10.1111/j.0006-341x.2000.00337.x · Cited by 2,870
Nivolumab and ipilimumab versus ipilimumab in untreated melanoma
Postow, M. A., Chesney, J., Pavlick, A. C., Robert, C., Grossmann, K., McDermott, D., Linette, G. P., Meyer, N., Giguere, J. K., Agarwala, S. S., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1414428 · Cited by 2,781 · cited 8×
“Asthenia 30 (10) 1 (<1) 25 (8) 1 (<1) 17 (5) 2 (1)”
InfluentialSelf-citation
Research works printed but not linked: 2
- Robert C, 2017, J Clin Oncol, 15, 35
- Long GV, Ann Oncol
Cited by
Sorted by citations
Items 201–300 of 1,021
Abdel-Hakeem, M. S., Manne, S., Beltra, J., Stelekati, E., Chen, Z., Nzingha, K., Ali, M.-A., Johnson, J. L., Giles, J. R., Mathew, D., et al. (2021) · Nature Immunology · doi:10.1038/s41590-021-00975-5 · Cited by 252
Zhou, X., Yao, Z., Bai, H., Duan, J., Wang, Z., Wang, X., Zhang, X., Xu, J., Fei, K., Zhang, Z., et al. (2021) · The Lancet Oncology · doi:10.1016/s1470-2045(21)00333-8 · Cited by 261
Hoch, T., Schulz, D., Eling, N., Gómez, J. M. M., Levesque, M. P., & Bodenmiller, B. (2022) · Science Immunology · doi:10.1126/sciimmunol.abk1692 · Cited by 253
Tumor immune microenvironment lncRNAs
Park, E.-G., Pyo, S.-J., Cui, Y., Yoon, S.-H., & Nam, J. (2021) · Briefings in Bioinformatics · doi:10.1093/bib/bbab504 · Cited by 253
Five-Year Outcomes With Nivolumab in Patients With Wild-Type BRAF Advanced Melanoma
Robert, C., Long, G. V., Brady, B., Dutriaux, C., Giacomo, A. M. D., Mortier, L., Rutkowski, P. L., Hassel, J. C., McNeil, C. M., Kalinka‐Warzocha, E., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.20.00995 · Cited by 259
“When an anti–PD-1 agent is combined with ipilimumab, as in CheckMate 067, a numerically greater survival benefit (52% at 5 years) was observed but with increased toxicity to some patients.(2,5,11,12) Thus, it would be critically useful to have reliable predictive parameters to guide patient selection, but to date, thi…”
BackgroundSelf-citationTranslational advances in pancreatic ductal adenocarcinoma therapy
Hosein, A. N., Dougan, S. K., Aguirre, A. J., & Maitra, A. (2022) · Nature Cancer · doi:10.1038/s43018-022-00349-2 · Cited by 255
Collier, J. L., Weiss, S. A., Pauken, K. E., Sen, D. R., & Sharpe, A. H. (2021) · Nature Immunology · doi:10.1038/s41590-021-00949-7 · Cited by 237
Boyer, M. J., Şendur, M. A. N., Rodríguez‐Abreu, D., Park, K., Lee, D. H., Çiçin, İ., Yumuk, P. F., Orlandi, F., Leal, T. A. B., Molinier, O., et al. (2021) · Journal of Clinical Oncology · doi:10.1200/jco.20.03579 · Cited by 253
“The median (range) number of treatment cycles was 10 (1-35) in the pembrolizumabipilimumab group and 15 (1-35) in the pembrolizumabplacebo group (Appendix Table A2, online only).”
BackgroundClinical cancer immunotherapy: Current progress and prospects
Liu, C., Yang, M., Zhang, D., Chen, M., & Zhu, D. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.961805 · Cited by 261
Cella, D. F., Grünwald, V., Escudier, B. J., Hammers, H. J., George, S., Nathan, P., Grimm, M., Rini, B. I., Doan, J. F., Ivanescu, C., et al. (2019) · The Lancet Oncology · doi:10.1016/s1470-2045(18)30778-2 · Cited by 253
Trial watch: TLR3 agonists in cancer therapy
Le Naour, J., Galluzzi, L., Zitvogel, L., Kroemer, G., & Vacchelli, E. (2020) · OncoImmunology · doi:10.1080/2162402x.2020.1771143 · Cited by 239
Khair, D. O., Bax, H. J., Mele, S., Crescioli, S., Pellizzari, G., Khiabany, A., Nakamura, M., Harris, R. J. C., French, E., Hoffmann, R. M., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00453 · Cited by 252
“5 months and 3-year overall survival (OS) rates of 52, 34, and 58%, respectively (52).”
BackgroundResultInfluentialCouey, M., Bell, R. B., Patel, A., Romba, M. C., Crittenden, M. R., Curti, B. D., Urba, W. J., & Leidner, R. S. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0645-6 · Cited by 249
Self‐Amplified Drug Delivery with Light‐Inducible Nanocargoes to Enhance Cancer Immunotherapy
Feng, B., Hou, B., Xu, Z., Saeed, M., Yu, H., & Li, Y. (2019) · Advanced Materials · doi:10.1002/adma.201902960 · Cited by 245
Kim, C. G., Jang, M., Kim, Y., Leem, G., Kim, K. H., Lee, H., Kim, T.-S., Choi, S. J., Kim, H.-D., Han, J. W., et al. (2019) · Science Immunology · doi:10.1126/sciimmunol.aay0555 · Cited by 245
Cichocki, F. M., Bjordahl, R., Gaidarova, S., Mahmood, S., Abujarour, R., Wang, H., Tuininga, K., Felices, M., Davis, Z., Bendzick, L. E., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aaz5618 · Cited by 249
Progress and challenges of immunotherapy in triple-negative breast cancer
Zhu, Y., Zhu, X., Tang, C., Guan, X., & Zhang, W. (2021) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2021.188593 · Cited by 242
Wang, Y., Abu‐Sbeih, H., Mao, E., Ali, N., Ali, F. S., Qiao, W., Lum, P. J., Raju, G. S., Shuttlesworth, G. A., Stroehlein, J., et al. (2018) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-018-0346-6 · Cited by 244
“As shown in Table 4, as well as reported in previously published studies, [6, 28] among all ICPIs, CTLA-4 agents (e.”
ResultZimmer, L., Livingstone, E., Hassel, J. C., Fluck, M., Eigentler, T., Loquai, C., Haferkamp, S., Gutzmer, R., Meier, F. E., Mohr, P., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30417-7 · Cited by 251
Self-citationPaver, E. C., Cooper, W. A., Colebatch, A. J., Ferguson, P. M., Hill, S. K., Lum, T., Shin, J., O’Toole, S. A., Anderson, L. A., Scolyer, R. A., et al. (2020) · Pathology · doi:10.1016/j.pathol.2020.10.007 · Cited by 252
Autoimmunity, checkpoint inhibitor therapy and immune-related adverse events: A review
Khan, S., & Gerber, D. E. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.06.012 · Cited by 250
“With combination anti-CTLA4 and antiPD-1 therapy, almost 60% of patients achieve a radiographic response, with median average survival exceeding 3 years [28, 29].”
BackgroundHot and cold tumors: Immunological features and the therapeutic strategies
Wang, L., Geng, H., Liu, Y., Liu, L., Chen, Y., Wu, F., Liu, Z., Ling, S., Wang, Y., & Zhou, L. (2023) · MedComm · doi:10.1002/mco2.343 · Cited by 261
Sharma, P., Siefker-Radtke, A. O., de Braud, F., Basso, U., Calvo, E., Bono, P., Morse, M. A., Ascierto, P. A., Lopez-Martin, J. A., Brossart, P., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.19.00538 · Cited by 244
“reported safety profile of nivolumab monotherapy in CheckMate 032,(16) and the incidence of certain AEs was consistent with the safety profiles of nivolumab plus ipilimumab in other cancer types.(11,14) However, the incidence of high-grade TRAEs or high-grade treatment-related select AEs and the use of immune-modulati…”
BackgroundResultInfluentialSelf-citationTreatment of Glioblastoma (GBM) with the Addition of Tumor-Treating Fields (TTF): A Review
Fabian, D., Eibl, M. D. P. G. P., Alnahhas, I., Sebastian, N., Giglio, P., Puduvalli, V. K., Gonzalez, J., & Palmer, J. D. (2019) · Cancers · doi:10.3390/cancers11020174 · Cited by 249
“5 months with combination therapy [36].”
Mechanisms of immune activation and regulation: lessons from melanoma
Kalaora, S., Nagler, A., Wargo, J. A., & Samuels, Y. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00442-9 · Cited by 252
Immune checkpoints in the tumor microenvironment
Toor, S. M., Nair, V. S., Decock, J. V., & Elkord, E. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.06.021 · Cited by 242
Tumour mutational burden as a biomarker for immunotherapy: Current data and emerging concepts
Fumet, J.-D., Truntzer, C., Yarchoan, M. M., & Ghiringhelli, F. (2020) · European Journal of Cancer · doi:10.1016/j.ejca.2020.02.038 · Cited by 242
Learning from clinical trials of neoadjuvant checkpoint blockade
Versluis, J. M., Long, G. V., & Blank, C. U. (2020) · Nature Medicine · doi:10.1038/s41591-020-0829-0 · Cited by 234
Self-citationKeilholz, U., Ascierto, P. A., Dummer, R., Robert, C., Lorigan, P. C., van Akkooi, A. C. J., Arance, A. M., Blank, C. U., Chiarion‐Sileni, V., Donia, M., et al. (2020) · Annals of Oncology · doi:10.1016/j.annonc.2020.07.004 · Cited by 242
Self-citationVirassamy, B., Caramia, F., Savas, P. S., Sant, S. A., Wang, J., Christo, S. N., Byrne, A., Clarke, K. A., Brown, E., Teo, Z. L., et al. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.01.004 · Cited by 247
Cell membrane coated-nanoparticles for cancer immunotherapy
Zeng, Y., Li, S., Zhang, S., Wang, L., Yuan, H., & Hu, F. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.02.023 · Cited by 238
Li, Y., Su, Z., Zhao, W., Zhang, X., Momin, N., Zhang, C., Wittrup, K. D., Dong, Y., Irvine, D. J., & Weiss, R. (2020) · Nature Cancer · doi:10.1038/s43018-020-0095-6 · Cited by 233
Klein, O., Kee, D., Nagrial, A. M., Markman, B., Underhill, C. R., Michael, M., Jackett, L. A., Lum, C., Behren, A., Palmer, J., et al. (2020) · JAMA Oncology · doi:10.1001/jamaoncol.2020.2814 · Cited by 232
Self-citationMoik, F., Chan, W.-S. E., Wiedemann, S., Höeller, C., Tuchmann, F., Aretin, M., Fuereder, T., Zöchbauer‐Müller, S., Preusser, M., Pabinger, I., et al. (2020) · Blood · doi:10.1182/blood.2020007878 · Cited by 235
Systemic Therapy for Melanoma: ASCO Guideline Update
Seth, R., Agarwala, S. S., Messersmith, H. J., Alluri, K. C., Ascierto, P. A., Atkins, M. B., Bollin, K. B., Chacon, M. R., Davis, N. B., Faries, M. B., et al. (2023) · Journal of Clinical Oncology · doi:10.1200/jco.23.01136 · Cited by 251
Self-citationCruz, E., & Kayser, V. (2019) · Biologics · doi:10.2147/btt.s166310 · Cited by 245
“Notwithstanding, combined therapy also seems to increase the frequency of immune-related toxicities.(127) Thorough reviews on strategies and novel concepts for combination therapy can be found in.”
BackgroundComprehensive Analysis of Cuproptosis-Related Genes in Immune Infiltration and Prognosis in Melanoma
Lv, H., Liu, X., Zeng, X., Liu, Y., Zhang, C.-J., Zhang, Q., & Xu, J. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.930041 · Cited by 233
Rational design of anti-GITR-based combination immunotherapy
Zappasodi, R., Sirard, C. A., Li, Y., Budhu, S., Abu-Akeel, M., Liu, C., Yang, X., Zhong, H., Newman, W., Qi, J., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0420-8 · Cited by 233
Self-citationJansen, Y. J. L., Rozeman, E. A., Mason, R., Goldinger, S. M., Foppen, M. H. G., Hoejberg, L., Schmidt, H., van Thienen, J. V., Haanen, J. B. A. G., Tiainen, L., et al. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz110 · Cited by 229
“In the phase III KEYNOTE-006 trial, 103 patients discontinued pembrolizumab after the foreseen maximum duration of 24 months of which, 19 (18”
BackgroundResultInfluentialSelf-citationPelly, V. S., Moeini, A., Roelofsen, L. M., Bonavita, E., Bell, C. R., Hutton, C., Blanco‐Gómez, A., Banyard, A., Bromley, C. P., Flanagan, E., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1815 · Cited by 230
Pembrolizumab Plus Ipilimumab Following Anti-PD-1/L1 Failure in Melanoma
Olson, D. J., Eroglu, Z., Brockstein, B., Poklepovic, A. S., Bajaj, M., Babu, S., Hallmeyer, S., Velasco, M. R., Lutzky, J., Higgs, E. F., et al. (2021) · Journal of Clinical Oncology · doi:10.1200/jco.21.00079 · Cited by 230
Haen, S. P., Loeffler, M. W., Rammensee, H., & Brossart, P. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0387-x · Cited by 241
Overcoming Immune Evasion in Melanoma
Eddy, K., & Chen, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21238984 · Cited by 243
da Silva, I. P., Ahmed, T., Reijers, I. L. M., Weppler, A. M., Warner, A. B., Patrinely, J. R., Serra-Bellver, P., Allayous, C., Mangana, J., Nguyen, K., et al. (2021) · The Lancet Oncology · doi:10.1016/s1470-2045(21)00097-8 · Cited by 229
Self-citationNanoparticle‐based photothermal and photodynamic immunotherapy for tumor treatment
Hou, X., Tao, Y., Pang, Y., Li, X., Jiang, G., & Liu, Y. (2018) · International Journal of Cancer · doi:10.1002/ijc.31717 · Cited by 223
“However, the simultaneous use of anti-CTLA-4 and anti-PD-1 in combination with PTT accelerates the death of tumor-bearing mice(46) possibly because combined therapy with anti-CTLA-4 and anti-PD-1 is likely to trigger treatmentrelated adverse events of grade 3 or 4.(72) This finding highlights that the complexity and s…”
BackgroundPD-1/PD-L1 Targeting in Breast Cancer: The First Clinical Evidences are Emerging—A Literature Review
Planes-Laine, G., Rochigneux, P., Bertucci, F., Chrétien, A.-S., Viens, P., Sabatier, R., & Gonçalvès, A. (2019) · Cancers · doi:10.3390/cancers11071033 · Cited by 227
“…reasons: (i) a biological rationale suggesting a synergy between anti-CTLA-4 (activating the T cells in the lymph node) and anti-PD(L)-1 (activating the T cells in the tumor site); and (ii) the successful ipilimumab / nivolumab association in melanoma [115] and in NSCLCC TMB high patients [107].”
BackgroundDiab, A., Tannir, N. M., Bentebibel, S.-E., Hwu, P., Papadimitrakopoulou, V., Haymaker, C., Kluger, H. M., Gettinger, S. N., Sznol, M., Tykodi, S. S., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-1510 · Cited by 237
“A lower neutrophil to lymphocyte ratio has been identified as a potential biomarker for response to CPIs (29).”
ResultInfluentialMolecular Markers and Targets in Melanoma
Teixidó, C., Castillo, P., Martínez-Vila, C., Arance, A. M., & Alós, L. (2021) · Cells · doi:10.3390/cells10092320 · Cited by 262
Elkrief, A., El Raichani, L., Richard, C., Messaoudene, M., Belkaid, W., Malo, J., Belanger, K., Miller, W., Jamal, R., Letarte, N., et al. (2019) · OncoImmunology · doi:10.1080/2162402x.2019.1568812 · Cited by 208
“Combinations of ICIs provide deeper response rates; however, toxicities remain the principal hurdle.(5) Now, the use of ICIs in both neoadjuvant and adjuvant settings represent a promising therapeutic avenue for patients with high-risk locally advanced melanoma.”
BackgroundBuder‐Bakhaya, K., & Hassel, J. C. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01474 · Cited by 219
“Although not designed for this purpose, this study revealed that patients with tumors expressing PD-L1 had similar PFS and OS compared with PD1ab monotherapy and the combination of CTLA4ab plus PD1ab (5, 114).”
BackgroundResultRecurrent Glioblastoma: From Molecular Landscape to New Treatment Perspectives
Birzu, C., French, P. J., Caccese, M., Cerretti, G., Idbaïh, A., Zagonel, V., & Lombardi, G. (2020) · Cancers · doi:10.3390/cancers13010047 · Cited by 229
Pal, S. K., Albiges, L. K., Tomczak, P., Suárez, C., Voss, M. H., de Velasco, G., Chahoud, J., Mochalova, A. S., Procopio, G., Mahammedi, H., et al. (2023) · The Lancet · doi:10.1016/s0140-6736(23)00922-4 · Cited by 230
Gao, X., Xu, N., Li, Z., Shen, L., Ji, K., Zheng, Z., Liu, D., Lou, H., Bai, L., Liu, T., et al. (2023) · The Lancet Oncology · doi:10.1016/s1470-2045(23)00411-4 · Cited by 226
Kjeldsen, J. W., Lorentzen, C. L., Martinenaite, E., Ellebæk, E., Donia, M., Holmstroem, R. B., Klausen, T. W., Madsen, C. O., Ahmed, S. M., Weis-Banke, S. E., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01544-x · Cited by 215
Recent advances in systemic therapy for hepatocellular carcinoma
Zhang, H., Zhang, W., Jiang, L., & Chen, Y. (2022) · Biomarker Research · doi:10.1186/s40364-021-00350-4 · Cited by 218
Cutaneous melanoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
Amaral, T. M. S., Ottaviano, M., Arance, A. M., Blank, C. U., Chiarion‐Sileni, V., Donia, M., Dummer, R., Garbe, C., Gershenwald, J. E., Gogas, H. J., et al. (2024) · Annals of Oncology · doi:10.1016/j.annonc.2024.11.006 · Cited by 248
Self-citationAbu-Sbeih, H., Ali, F. S., Alsaadi, D., Jennings, J., Luo, W., Gong, Z., Richards, D. M., Charabaty, A., & Wang, Y. (2018) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-018-0461-4 · Cited by 215
Emerging strategies for combination checkpoint modulators in cancer immunotherapy
Popović, A., Jaffee, E. M., & Zaidi, N. (2018) · Journal of Clinical Investigation · doi:10.1172/jci120775 · Cited by 209
Noman, M. Z., Hasmim, M., Lequeux, A., Xiao, M., Duhem, C., Chouaı̈b, S., Berchem, G., & Janji, B. (2019) · Cells · doi:10.3390/cells8091083 · Cited by 220
“However, combined therapy with both anti-PD-1 and anti-CTL-A4 significantly improves patient survival [10,11].”
BackgroundAdolescent and Young Adult (AYA) Cancer Survivorship Practices: An Overview
Janssen, S. H. M., van der Graaf, W. T. A., van der Meer, D. J., Manten‐Horst, E., & Husson, O. (2021) · Cancers · doi:10.3390/cancers13194847 · Cited by 216
Dual blockade immunotherapy targeting PD-1/PD-L1 and CTLA-4 in lung cancer
Cheng, W., Kang, K., Zhao, A., & Wu, Y. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01581-2 · Cited by 229
Suzman, D. L., Pelosof, L., Rosenberg, A., & Avigan, M. I. (2018) · Liver International · doi:10.1111/liv.13746 · Cited by 189
Bispecific antibodies in cancer immunotherapy
Dahlén, E., Veitonmäki, N., & Norlén, P. (2018) · Therapeutic Advances in Vaccines and Immunotherapy · doi:10.1177/2515135518763280 · Cited by 215
“(1) Cytotoxic effector cell redirectors, including (a) T-cell redirectors (b) NK-cell redirectors (2) Tumor-targeted immunomodulators (3) Dual immunomodulators.”
BackgroundAn expanded universe of cancer targets
Hahn, W. C., Bader, J. S., Braun, T. P., Califano, A., Clemons, P. A., Druker, B. J., Ewald, A. J., Fu, H., Jagu, S., Kemp, C. J., et al. (2021) · Cell · doi:10.1016/j.cell.2021.02.020 · Cited by 213
Immune cell - produced ROS and their impact on tumor growth and metastasis
Kennel, K. B., & Greten, F. R. (2021) · Redox Biology · doi:10.1016/j.redox.2021.101891 · Cited by 213
Immune Checkpoint Inhibitor Therapy in Oncology
Tan, S., Day, D., Nicholls, S. J., & Segelov, E. (2022) · JACC CardioOncology · doi:10.1016/j.jaccao.2022.09.004 · Cited by 219
Abu-Sbeih, H., Ali, F. S., Luo, W., Qiao, W., Raju, G. S., & Wang, Y. (2018) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-018-0411-1 · Cited by 209
Willsmore, Z. N., Coumbe, B. G. T., Crescioli, S., Reci, S., Gupta, A., Harris, R. J. C., Chenoweth, A. M., Chauhan, J., Bax, H. J., McCraw, A. J., et al. (2021) · European Journal of Immunology · doi:10.1002/eji.202048747 · Cited by 216
Melanoma models for the next generation of therapies
Patton, E. E., Mueller, K. L., Adams, D. J., Anandasabapathy, N., Aplin, A. E., Bertolotto, C., Bosenberg, M., Ceol, C. J., Burd, C. E., Chi, P., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.01.011 · Cited by 219
Treatment after progression in the era of immunotherapy
Billan, S., Kaidar‐Person, O., & Gil, Z. (2020) · The Lancet Oncology · doi:10.1016/s1470-2045(20)30328-4 · Cited by 205
Wu, Q., Qian, W., Sun, X., & Jiang, S. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01362-9 · Cited by 208
A TCF4-dependent gene regulatory network confers resistance to immunotherapy in melanoma
Pozniak, J., Pedri, D., Landeloos, E., Van Herck, Y., Antoranz, A., Vanwynsberghe, L., Nowosad, A., Roda, N., Makhzami, S., Bervoets, G., et al. (2024) · Cell · doi:10.1016/j.cell.2023.11.037 · Cited by 199
Self-citationD’Angelo, S. P., Bhatia, S., Brohl, A. S., Hamid, O., Mehnert, J. M., Terheyden, P. A. M., Shih, K. C., Brownell, I., Lebbé, C., Lewis, K. D., et al. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-000674 · Cited by 207
Self-citationExpansion of tumor-associated Treg cells upon disruption of a CTLA-4-dependent feedback loop
Marangoni, F., Zhakyp, A., Corsini, M., Geels, S. N., Carrizosa, E., Thelen, M., Mani, V., Pruessmann, J. N., Warner, R. D., Ozga, A. J., et al. (2021) · Cell · doi:10.1016/j.cell.2021.05.027 · Cited by 209
The Use of Immune Checkpoint Inhibitors in Oncology and the Occurrence of AKI: Where Do We Stand?
Franzin, R., Netti, G. S., Spadaccino, F., Porta, C., Gesualdo, L., Stallone, G., Castellano, G., & Ranieri, E. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.574271 · Cited by 208
Lan, Y., Moustafa, M., Knoll, M., Xu, C., Furkel, J., Lazorchak, A. S., Yeung, T.-L., Hasheminasab, S.-M., Jenkins, M. H., Meister, S., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.08.008 · Cited by 211
Yang, J., & Hu, L. (2018) · Medicinal Research Reviews · doi:10.1002/med.21530 · Cited by 201
“6 months; 3‐year OS rate: 52%).(150,151) More recently, in the phase 2 trial CheckMate‐142, nivolumab and ipilimumab again exhibited high response rates (55%; 65 of 119 patients) and encouraging PFS (71%) and OS (85%) at 12 months in patients with dMMR/MSI‐H metastatic colorectal cancer.”
BackgroundForschner, A., Battke, F., Hadaschik, D., Schulze, M., Weißgraeber, S., Han, T., Kopp, M., Frick, M., Klumpp, B. D., Tietze, N., et al. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0659-0 · Cited by 215
Human Anti-tumor Immunity: Insights from Immunotherapy Clinical Trials
Egen, J. G., Ouyang, W., & Wu, L. C. (2020) · Immunity · doi:10.1016/j.immuni.2019.12.010 · Cited by 198
Adoptive transfer of tumor-infiltrating lymphocytes in melanoma: a viable treatment option
Rohaan, M. W., van den Berg, J. H., Kvistborg, P., & Haanen, J. B. A. G. (2018) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-018-0391-1 · Cited by 204
“Treatment with PD-1 blockade, or an anti-PD-1-based combination, is now mostly first-line therapy in patients with advanced melanoma, showing an unprecedented 3-year overall survival around 50% [4].”
BackgroundSelf-citationThe Immune Subtypes and Landscape of Squamous Cell Carcinoma
Li, B., Cui, Y., Nambiar, D. K., Sunwoo, J. B., & Li, R. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-4085 · Cited by 199
“In particular, immune 53 checkpoint blockade (ICB) such as anti-PD1 antibodies have demonstrated durable response and 54 unprecedented clinical benefit in a subset of patients across multiple types of solid tumors (1-6).”
BackgroundHaas, L., Elewaut, A., Gerard, C. L., Umkehrer, C., Leiendecker, L., Pedersen, M., Kręcioch, I., Hoffmann, D., Novatchkova, M., Kuttke, M., et al. (2021) · Nature Cancer · doi:10.1038/s43018-021-00221-9 · Cited by 196
Self-citationStudy and analysis of antitumor resistance mechanism of PD1/PD‐L1 immune checkpoint blocker
Wang, Z., & Wu, X. (2020) · Cancer Medicine · doi:10.1002/cam4.3410 · Cited by 205
Resistance mechanisms to immune checkpoint inhibitors: updated insights
Al-Saafeen, B. H., Ali, B. R., & Elkord, E. (2025) · Molecular Cancer · doi:10.1186/s12943-024-02212-7 · Cited by 226
“…upregulation of alternative immune check-point molecules is a potential target for immunotherapy combinations and the beneficial outcomes observed as a result of targeting multiple inhibitory immune check-points were demonstrated by undeniable number of pre-clinical and clinical studies [186–190].”
Ipilimumab and Gemcitabine for Advanced Pancreatic Cancer: A Phase Ib Study
Kamath, S. D., Kalyan, A., Kircher, S. M., Nimeiri, H. S., Fought, A. J., Benson, A. B., & Mulcahy, M. F. (2019) · The Oncologist · doi:10.1634/theoncologist.2019-0473 · Cited by 200
van den Berg, J. H., Heemskerk, B., van Rooij, N., Gomez-Eerland, R., Michels, S., van Zon, M., de Boer, R., Bakker, N. A. M., Jorritsma‐Smit, A., van Buuren, M. M., et al. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-000848 · Cited by 194
Self-citationJohnson, D. H., Zobniw, C. M., Trinh, V. A., Ma, J., Bassett, R. L., Abdel‐Wahab, N., Anderson, J. E., Davis, J. E., Joseph, J., Uemura, M. I., et al. (2018) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-018-0412-0 · Cited by 196
Tang, S., Tang, L., Mao, Y., Li, W., Chen, L., Zhang, Y., Guo, Y. Q., Liu, Q., Sun, Y. H., Xu, C., et al. (2020) · Cancer Research and Treatment · doi:10.4143/crt.2020.790 · Cited by 206
Ferrucci, P. F., Giacomo, A. M. D., Vecchio, M. D., Atkinson, V. G., Schmidt, H., Schachter, J., Queirolo, P., Long, G. V., Stephens, R., Svane, I. M., et al. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-001806 · Cited by 200
Self-citationMurakami, N., Mulvaney, P. M., Danesh, M. J., Abudayyeh, A., Diab, A. K., Abdel‐Wahab, N., Abdelrahim, M., Khairallah, P., Shirazian, S., Kukla, A., et al. (2020) · Kidney International · doi:10.1016/j.kint.2020.12.015 · Cited by 200
Self-citationO’Malley, D. M., Neffa, M., Monk, B. J., Melkadze, T., Huang, M., Kryzhanivska, A., Bulat, I., Meniawy, T. M., Bagameri, A., Wang, W., et al. (2021) · Journal of Clinical Oncology · doi:10.1200/jco.21.02067 · Cited by 193
“The incidence of grade 3 or higher TRAEs (20%) is similar to previous trials that led to the approval of the nivolumab-ipilimumab combination in nongynecologic malignancies.(34,37-40)”
ResultNew therapeutic perspectives to manage refractory immune checkpoint-related toxicities
Martins, F., Sykiotis, G. P., Maillard, M. H., Fraga, M. C., Ribi, C., Küntzer, T., Michielin, O. A., Peters, S., Coukos, G., Spertini, F., et al. (2019) · The Lancet Oncology · doi:10.1016/s1470-2045(18)30828-3 · Cited by 190
The Role of the Estrogen Pathway in the Tumor Microenvironment
Rothenberger, N. J., Somasundaram, A., & Stabile, L. P. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19020611 · Cited by 202
Regulation of Treg cells by cytokine signaling and co-stimulatory molecules
Zong, Y., Deng, K., & Chong, W. P. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1387975 · Cited by 202
Limeta, A., Ji, B., Levin, M., Gatto, F., & Nielsen, J. (2020) · JCI Insight · doi:10.1172/jci.insight.140940 · Cited by 185
Nakao, S., Arai, Y., Tasaki, M., YAMASHITA, M., Murakami, R., Kawase, T., Amino, N., Nakatake, M., Kurosaki, H., Mori, M., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aax7992 · Cited by 192
Immune checkpoint inhibitor‐induced Type 1 diabetes: a systematic review and meta‐analysis
Aktürk, H. K., Kahramangil, D., Sarwal, A., Hoffecker, L., Murad, M. H., & Michels, A. W. (2019) · Diabetic Medicine · doi:10.1111/dme.14050 · Cited by 195
Frank, M. J., Reagan, P. M., Bartlett, N. L., Gordon, L. I., Friedberg, J. W., Czerwinski, D. K., Long, S., Hoppe, R. T., Janssen, R. S., Candia, A. F., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0743 · Cited by 190
Prediction and monitoring of relapse in stage III melanoma using circulating tumor DNA
Tan, L., Sandhu, S. K., Lee, R. J., Li, J., Callahan, J., Ftouni, S., Dhomen, N. S., Middlehurst, P., Wallace, A. J., Raleigh, J., et al. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz048 · Cited by 196
Self-citationZhai, Y., Ye, X., Hu, F., Xu, J., Guo, X., Zhuang, Y., & He, J. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0754-2 · Cited by 195
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
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
