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 account Open 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

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

Crossref · 10.1056/nejmoa1801946

Cites

22 of 22 references verified0 citation errors · 0 not checkable

Statistics

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?

Self-check

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

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

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
Toxicity and response criteria of the Eastern Cooperative Oncology Group
Oken, M. M., Creech, R. H., Tormey, D. C., Horton, J., Davis, T. E., Mcfadden, E. T., & Carbone, P. P. (1982) · American Journal of Clinical Oncology · doi:10.1097/00000421-198212000-00014 · Cited by 11,686
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
Self-citation
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
Self-citation
Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade
Le, D. T., Durham, J. N., Smith, K. N., Wang, H., Bartlett, B. R., Aulakh, L. K., Lu, S., Kemberling, H., Wilt, C., Luber, B. S., et al. (2017) · Science · doi:10.1126/science.aan6733 · Cited by 6,645
Self-citation
Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma
Snyder, A., Makarov, V., Merghoub, T., Yuan, J., Zaretsky, J. M., Desrichard, A., Walsh, L. A., Postow, M. A., Wong, P., Ho, T. S., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1406498 · Cited by 4,286
Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial
Rosenberg, J. E., Hoffman-Censits, J., Powles, T., van der Heijden, M. S., Balar, A. V., Necchi, A., Dawson, N., O'Donnell, P. H., Balmanoukian, A., Loriot, Y., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00561-4 · Cited by 3,669
Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden
Chalmers, Z. R., Connelly, C. F., Fabrizio, D., Gay, L., Ali, S. M., Ennis, R., Schrock, A., Campbell, B., Shlien, A., Chmielecki, J., et al. (2017) · Genome Medicine · doi:10.1186/s13073-017-0424-2 · Cited by 3,519
Tumor mutational burden and response rate to PD-1 inhibition
Yarchoan, M., Hopkins, A., & Jaffee, E. M. (2017) · New England Journal of Medicine · doi:10.1056/nejmc1713444 · Cited by 3,230
Genomic correlates of response to CTLA-4 blockade in metastatic melanoma
Van Allen, E. M., Miao, D., Schilling, B., Shukla, S. A., Blank, C., Zimmer, L., Sucker, A., Hillen, U., Geukes Foppen, M. H., Goldinger, S. M., et al. (2015) · Science · doi:10.1126/science.aad0095 · Cited by 2,839

Show all 22 references

Sorted by citations

Items 601–700 of 1,002

Clinical Utility of Liquid Biopsy-Based Actionable Mutations Detected via ddPCR
Palacín-Aliana, I., Garcia‐Romero, N., Asensi-Puig, A., Carrión-Navarro, J., González‐Rumayor, V., & Ayuso‐Sacido, Á. (2021) · Biomedicines · doi:10.3390/biomedicines9080906 · Cited by 63
Germline modifiers of the tumor immune microenvironment implicate drivers of cancer risk and immunotherapy response
Pagadala, M. S., Sears, T. J., Wu, V. H., Pérez‐Guijarro, E., Kim, H., Castro, A., Talwar, J. V., González-Colín, C., Cao, S., Schmiedel, B. J., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38271-5 · Cited by 54
Durvalumab ± Tremelimumab + Platinum-Etoposide in Extensive-Stage Small Cell Lung Cancer (CASPIAN): Outcomes by PD-L1 Expression and Tissue Tumor Mutational Burden
Paz-Ares, L. G., Garassino, M. C., Chen, Y., Reinmuth, N., Hotta, K., Poltoratskiy, A., Trukhin, D. V., Hochmair, M. J., Özgüroğlu, M., Ji, J. H., et al. (2023) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-23-1689 · Cited by 63
Self-citation
Risk of immune-related adverse events associated with ipilimumab-plus-nivolumab and nivolumab therapy in cancer patients
Zhou, S., Khanal, S., & Zhang, H. (2019) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s193338 · Cited by 58
First-Line Treatment of Non-Small-Cell Lung Cancer (NSCLC) with Immune Checkpoint Inhibitors
Bylicki, O., Barazzutti, H., Paleiron, N., Margery, J., Assié, J., & CHOUAID, C. (2019) · BioDrugs · doi:10.1007/s40259-019-00339-4 · Cited by 60
The evolving immuno-oncology landscape in advanced lung cancer: first-line treatment of non-small cell lung cancer
Low, J. L., Walsh, R. J., Ang, Y. L. E., Chan, G. H. J., & Soo, R. A. (2019) · Therapeutic Advances in Medical Oncology · doi:10.1177/1758835919870360 · Cited by 59
Immunotherapy: From Advanced NSCLC to Early Stages, an Evolving Concept
Berghmans, T., Durieux, V., Hendriks, L. E. L., & Dingemans, A. C. (2020) · Frontiers in Medicine · doi:10.3389/fmed.2020.00090 · Cited by 58
Converging focal radiation and immunotherapy in a preclinical model of triple negative breast cancer: contribution of VISTA blockade
Pilones, K. A., Hensler, M., Daviaud, C., Kraynak, J., Fucikova, J. P., Galluzzi, L., Demaria, S., & Formenti, S. C. (2020) · OncoImmunology · doi:10.1080/2162402x.2020.1830524 · Cited by 59
DNA Mismatch Repair Deficiency and Immune Checkpoint Inhibitors in Gastrointestinal Cancers
Bañobre, J. R., & Goel, A. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.11.071 · Cited by 58
Immune Checkpoint Inhibitors-Related Thyroid Dysfunction: Epidemiology, Clinical Presentation, Possible Pathogenesis, and Management
Zhan, L., Feng, H.-F., Liu, H., Guo, L., Chen, C., Yao, X.-L., & Sun, S. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.649863 · Cited by 62
Prognostic Factors for Checkpoint Inhibitor Based Immunotherapy: An Update With New Evidences
Yan, X., Zhang, S., Deng, Y., Wang, P., Hou, Q., & Xu, H. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01050 · Cited by 59
Tumor PD-L1 expression in malignant pleural and peritoneal mesothelioma by Dako PD-L1 22C3 pharmDx and Dako PD-L1 28-8 pharmDx assays
Chapel, D. B., Stewart, R. L., Furtado, L. V., Husain, A. N., Krausz, T. N., & Deftereos, G. (2019) · Human Pathology · doi:10.1016/j.humpath.2019.02.001 · Cited by 57
Effect of sex on the efficacy of patients receiving immune checkpoint inhibitors in advanced non‐small cell lung cancer
Wang, C., Qiao, W., Jiang, Y., Zhu, M., Shao, J., Ren, P., Liu, D., & Li, W. (2019) · Cancer Medicine · doi:10.1002/cam4.2280 · Cited by 59
Comparative Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Advanced Cancer: A Systematic Review and Meta-Analysis
Yang, Y., Jin, G., Pang, Y., Huang, Y., Wang, W., Zhang, H., Tuo, G., Wu, P., Wang, Z., & Zhu, Z. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00040 · Cited by 61
Efficacy and safety of immune checkpoint inhibitors in patients with advanced non–small cell lung cancer (NSCLC): a systematic literature review
Wagner, G., Stollenwerk, H. K., Klerings, I., Pecherstorfer, M., Gartlehner, G., & Singer, J. (2020) · OncoImmunology · doi:10.1080/2162402x.2020.1774314 · Cited by 60
Machine learning reveals a PD-L1–independent prediction of response to immunotherapy of non-small cell lung cancer by gene expression context
Wiesweg, M., Mairinger, F. D., Reis, H., Goetz, M., Kollmeier, J., Misch, D., Stephan-Falkenau, S., Mairinger, T., Walter, R. F. H., Hager, T., et al. (2020) · European Journal of Cancer · doi:10.1016/j.ejca.2020.09.015 · Cited by 56
Development and Preliminary Clinical Activity of PD-1-Guided CTLA-4 Blocking Bispecific DART Molecule
Berezhnoy, A., Sumrow, B. J., Stahl, K., Shah, K., Liu, D., Li, J., Hao, S.-S., De Costa, A., Kaul, S., Bendell, J., et al. (2020) · Cell Reports Medicine · doi:10.1016/j.xcrm.2020.100163 · Cited by 56
Pneumonitis Induced by Immune Checkpoint Inhibitors: From Clinical Data to Translational Investigation
Zhu, S., Fu, Y., Zhu, B., Zhang, B., & Wang, J. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.01785 · Cited by 56
Self-citation
Pharmacology-based ranking of anti-cancer drugs to guide clinical development of cancer immunotherapy combinations
Lemaire, V., Shemesh, C. S., & Rotte, A. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-02111-5 · Cited by 56
A mutation-based gene set predicts survival benefit after immunotherapy across multiple cancers and reveals the immune response landscape
Long, J., Wang, D., Wang, A., Chen, P., Lin, Y. S., Bian, J., Yang, X., Zheng, M., Zhang, H., Zheng, Y., et al. (2022) · Genome Medicine · doi:10.1186/s13073-022-01024-y · Cited by 55
Machine learning for prediction of immunotherapeutic outcome in non-small-cell lung cancer based on circulating cytokine signatures
Wei, F., Azuma, K., Nakahara, Y., Saito, H., Matsuo, N., Tagami, T., Kouro, T., Igarashi, Y., Tokito, T., Kato, T., et al. (2023) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2023-006788 · Cited by 58
Evaluation of a Hybrid Capture–Based Pan-Cancer Panel for Analysis of Treatment Stratifying Oncogenic Aberrations and Processes
Kroeze, L. I., de Voer, R. M., Kamping, E. J., von Rhein, D. T., Jansen, E. A. M., Hermsen, M. J. W., Barberis, M. C. P., Botling, J., Garrido-Martin, E. M., Haller, F., et al. (2020) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2020.02.009 · Cited by 57
Choosing tumor mutational burden wisely for immunotherapy: A hard road to explore
Li, R., Han, D., Shi, J., Han, Y., Tan, P., Zhang, R., & Li, J. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188420 · Cited by 57
Therapeutic applications of the cancer immunoediting hypothesis
Desai, R. R., Coxon, A. T., & Dunn, G. P. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.03.002 · Cited by 59
TMB in NSCLC: A Broken Dream?
Bravaccini, S., Bronte, G., & Ulivi, P. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126536 · Cited by 60
Tumor Mutation Burden and Immune Invasion Characteristics in Triple Negative Breast Cancer: Genome High-Throughput Data Analysis
Gao, C., Li, H., Liu, C., Xu, X., Zhuang, J., Zhou, C., Liu, L., Feng, F., & Sun, C. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.650491 · Cited by 56
Antibody-drug conjugates, immune-checkpoint inhibitors, and their combination in breast cancer therapeutics
Saini, K. S., Punie, K., Twelves, C. J., Bortini, S., de Azambuja, E., Anderson, S., Criscitiello, C., Awada, A. H., & Loi, S. (2021) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2021.1936494 · Cited by 58
Immune checkpoint inhibitor treatment in patients with oncogene-addicted non-small cell lung cancer (NSCLC): summary of a multidisciplinary round-table discussion
Berghoff, A. S., Bellosillo, B., Caux, C., Langen, A. J. D., Mazières, J., Normanno, N., Preusser, M., Provencio, M., Rojo, F., Wolf, J., et al. (2019) · ESMO Open · doi:10.1136/esmoopen-2019-000498 · Cited by 56
Immune Checkpoint Inhibitors as Switch or Continuation Maintenance Therapy in Solid Tumors: Rationale and Current State
Grivas, P. D., Monk, B. J., Petrylak, D. P., Reck, M., Foley, G., Guenther, S., Hennessy, D., Makris, C., & Moehler, M. H. (2019) · Targeted Oncology · doi:10.1007/s11523-019-00665-1 · Cited by 56
Self-citation
A pilot trial of pembrolizumab plus prostatic cryotherapy for men with newly diagnosed oligometastatic hormone-sensitive prostate cancer
Ross, A. E., Hurley, P. J., Tran, P. T., Rowe, S. P., Benzon, B., Neal, T. O., Chapman, C. G., Harb, R., Milman, Y., Trock, B. J., et al. (2019) · Prostate Cancer and Prostatic Diseases · doi:10.1038/s41391-019-0176-8 · Cited by 56
Therapeutic Monoclonal Antibodies Targeting Immune Checkpoints for the Treatment of Solid Tumors
Gravbrot, N., Gilbert-Gard, K., Mehta, P. P., Ghotmi, Y., Banerjee, M., Mazis, C. M., & Sundararajan, S. (2019) · Antibodies · doi:10.3390/antib8040051 · Cited by 57
Prognostic value of immune score in nasopharyngeal carcinoma using digital pathology
Wang, Y., Chen, L., Mao, Y., Li, Y.-Q., Jiang, W., Xu, S., Zhang, Y., Chen, Y., Li, X., He, Q., et al. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2019-000334 · Cited by 55
Immune-Related Adverse Events and Corticosteroid Use for Cancer-Related Symptoms Are Associated With Efficacy in Patients With Non-small Cell Lung Cancer Receiving Anti-PD-(L)1 Blockade Agents
Riudavets, M., Mosquera, J., García‐Campelo, R., Serra-López, J., Anguera, G., Gallardo, P., Sullivan, I., Joaquín, A. B., del Carpio, L. P., Barnadas, A., et al. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.01677 · Cited by 55
Nivolumab plus chemotherapy in first-line metastatic non-small-cell lung cancer: results of the phase III CheckMate 227 Part 2 trial
Borghaei, H., O'Byrne, K. J., Paz-Ares, L. G., Ciuleanu, T.-E., Yu, X., Płużański, A., Nagrial, A. M., Havel, L., Kowalyszyn, R. D., Audigier-Valette, C., et al. (2023) · ESMO Open · doi:10.1016/j.esmoop.2023.102065 · Cited by 57
Self-citation
Society for Immunotherapy of Cancer (SITC) consensus statement on essential biomarkers for immunotherapy clinical protocols
Cottrell, T. R., Lotze, M. T., Ali, A. M., Bifulco, C. B., Capitini, C. M., Chow, L. Q. M., Cillo, A. R., Collyar, D. E., Cope, L., Deutsch, J. S., et al. (2025) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2024-010928 · Cited by 65
Recent Advances in the Clinical Development of Immune Checkpoint Blockade Therapy for Mismatch Repair Proficient (pMMR)/non-MSI-H Metastatic Colorectal Cancer
Lee, J. J., & Chu, E. (2018) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2018.06.004 · Cited by 55
Self-citation
Nivolumab Plus Ipilimumab in Non-Small-Cell Lung Cancer
Reck, M., Borghaei, H., & O'Byrne, K. J. (2019) · Future Oncology · doi:10.2217/fon-2019-0031 · Cited by 56
Self-citation
Bioinformatic Methods and Bridging of Assay Results for Reliable Tumor Mutational Burden Assessment in Non-Small-Cell Lung Cancer
Han, C., Sasson, A., Srinivasan, S., Golhar, R., Greenawalt, D. M., Geese, W. J., Green, G. A., Zerba, K. E., Kirov, S. A., & Szustakowski, J. D. (2019) · Molecular Diagnosis & Therapy · doi:10.1007/s40291-019-00408-y · Cited by 56
Self-citation
Expression of PD-L1 in ovarian cancer and its synergistic antitumor effect with PARP inhibitor
Xue, C., Xu, Y., Ye, W., Xie, Q., Gao, H., Xu, B., Zhang, D., & Jiang, J. (2020) · Gynecologic Oncology · doi:10.1016/j.ygyno.2019.12.012 · Cited by 54
Harnessing cell-free DNA: plasma circulating tumour DNA for liquid biopsy in genitourinary cancers
Maia, M. C., Salgia, M. M., & Pal, S. K. (2020) · Nature Reviews Urology · doi:10.1038/s41585-020-0297-9 · Cited by 56
Beyond Tumor PD-L1: Emerging Genomic Biomarkers for Checkpoint Inhibitor Immunotherapy
Lagos, G., Izar, B., & Rizvi, N. A. (2020) · American Society of Clinical Oncology Educational Book · doi:10.1200/edbk_289967 · Cited by 54
Immunotherapy for non-small cell lung cancers: biomarkers for predicting responses and strategies to overcome resistance
Pu, X., Wu, L., Su, D., Mao, W., & Fang, B. (2018) · BMC Cancer · doi:10.1186/s12885-018-4990-5 · Cited by 56
Blood Predictive Biomarkers for Patients With Non–small-cell Lung Cancer Associated With Clinical Response to Nivolumab
Agulló-Ortuño, M. T., Gómez-Martín, Ó., Ponce, S., Iglesias, L., Ojeda, L., Ferrer, I., García‐Ruíz, I., Paz-Ares, L. G., & Pardo, V. (2019) · Clinical Lung Cancer · doi:10.1016/j.cllc.2019.08.006 · Cited by 53
Self-citation
Comprehensive analysis of POLE and POLD1 Gene Variations identifies cancer patients potentially benefit from immunotherapy in Chinese population
Yao, J., Gong, Y., Zhao, W., Han, Z., Guo, S., Liu, H., Peng, X., Xiao, W., Li, Y., Dang, S., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-52414-z · Cited by 53
Identifying predictors of HPV ‐related head and neck squamous cell carcinoma progression and survival through patient‐derived models
Facompre, N. D., Rajagopalan, P., Sahu, V., Pearson, A. T., Montone, K. T., James, C. D., Gleber‐Netto, F. O., Weinstein, G. S., Jalaly, J. B., Lin, A., et al. (2020) · International Journal of Cancer · doi:10.1002/ijc.33125 · Cited by 50
Current challenges for assessing the long-term clinical benefit of cancer immunotherapy: a multi-stakeholder perspective
Quinn, C., Garrison, L., Pownell, A., Atkins, M., de Pouvourville, G., Harrington, K., Ascierto, P., McEwan, P., Wagner, S., Borrill, J., et al. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-000648 · Cited by 49
Tumour neoantigen mimicry by microbial species in cancer immunotherapy
Boesch, M., Baty, F., Rothschild, S. I., Tamm, M., Joerger, M., Früh, M., & Brutsche, M. H. (2021) · British Journal of Cancer · doi:10.1038/s41416-021-01365-2 · Cited by 53
Circulating Biomarkers of Response and Toxicity of Immunotherapy in Advanced Non-Small Cell Lung Cancer (NSCLC): A Comprehensive Review
Indini, A., Rijavec, E., & Grossi, F. (2021) · Cancers · doi:10.3390/cancers13081794 · Cited by 54
Hypoxia-Related Radiomics and Immunotherapy Response: A Multicohort Study of Non-Small Cell Lung Cancer
Tunali, I., Tan, Y. Q., Gray, J. E., Katsoulakis, E., Eschrich, S. A., Saller, J. J., Aerts, H. J. W. L., Boyle, T. A., Qi, J., Güveniş, A., et al. (2021) · JNCI Cancer Spectrum · doi:10.1093/jncics/pkab048 · Cited by 54
A novel tumor mutational burden-based risk model predicts prognosis and correlates with immune infiltration in ovarian cancer
Wang, H., Liu, J., Jiang, Y., Wang, Z., Zhang, Z., Peng, J., Wang, Y., & Li, H. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.943389 · Cited by 54
Challenges in the treatment of small cell lung cancer in the era of immunotherapy and molecular classification
Caliman, E., Fancelli, S., Petroni, G., Michelet, M. R. G., Cosso, F., Ottanelli, C., Mazzoni, F., Voltolini, L., Pillozzi, S., & Antonuzzo, L. (2022) · Lung Cancer · doi:10.1016/j.lungcan.2022.11.014 · Cited by 54
Combination Immune Checkpoint Blockade Strategies to Maximize Immune Response in Gynecological Cancers
Liu, Y. L., & Zamarin, D. (2018) · Current Oncology Reports · doi:10.1007/s11912-018-0740-8 · Cited by 53
The innate immune architecture of lung tumors and its implication in disease progression
Milette, S., Fiset, P., Walsh, L. A., Spicer, J. D., & Quail, D. F. (2019) · The Journal of Pathology · doi:10.1002/path.5241 · Cited by 55
Tumor Mutational Burden Is Site Specific in Non–Small-Cell Lung Cancer and Is Highest in Lung Adenocarcinoma Brain Metastases
Stein, M. K., Pandey, M. K., Xiu, J., Tae, H., Swensen, J. J., Mittal, S., Brenner, A. J., Korn, W. M., Heimberger, A. B., & Martin, M. G. (2019) · JCO Precision Oncology · doi:10.1200/po.18.00376 · Cited by 54
Lung and Gut Microbiota as Potential Hidden Driver of Immunotherapy Efficacy in Lung Cancer
Carbone, C., Piro, G., Noia, V. D., D’Argento, E., Vita, E., Ferrara, M. G., Pilotto, S., Milella, M., Cammarota, G., Gasbarrini, A., et al. (2019) · Mediators of Inflammation · doi:10.1155/2019/7652014 · Cited by 54
Overcoming resistance to anti-PD1 and anti-PD-L1 treatment in gastrointestinal malignancies
Puccini, A., Battaglin, F., Iaia, M. L., Lenz, H., & Salem, M. E. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2019-000404 · Cited by 53
Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of severe gastrointestinal and hepatic toxicities from checkpoint inhibitors
Dougan, M. L., Blidner, A. G., Choi, J. N., Cooksley, T., Glezerman, I. G., Ginex, P., Girotra, M., Gupta, D., Johnson, D. B., Shannon, V. R., et al. (2020) · Supportive Care in Cancer · doi:10.1007/s00520-020-05707-3 · Cited by 53
Immune‐related adverse events of a PD‐L1 inhibitor plus chemotherapy versus a PD‐L1 inhibitor alone in first‐line treatment for advanced non–small cell lung cancer: A meta‐analysis of randomized control trials
Wang, M., Liang, H., Wang, W., Zhao, S., Cai, X., Zhao, Y., Li, C., Cheng, B., Xiong, S., Li, J., et al. (2020) · Cancer · doi:10.1002/cncr.33270 · Cited by 53
Immune Checkpoint Inhibitor Associated Hepatotoxicity in Primary Liver Cancer Versus Other Cancers: A Systematic Review and Meta‐Analysis
Fu, J., Li, W., McGrath, N., Lai, C. W., Brar, G., Xiang, Y., & Xie, C. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.650292 · Cited by 53
Veliparib in Combination With Platinum-Based Chemotherapy for First-Line Treatment of Advanced Squamous Cell Lung Cancer: A Randomized, Multicenter Phase III Study
Ramalingam, S. S., Novello, S., Guclu, S. Z., Bentsion, D., Zvirbule, Z., Szilasi, M., Bernabé, R., Syrigos, K., Byers, L. A., Clingan, P., et al. (2021) · Journal of Clinical Oncology · doi:10.1200/jco.20.03318 · Cited by 52
Self-citation
A scalable high-throughput targeted next-generation sequencing assay for comprehensive genomic profiling of solid tumors
Conroy, J. M., Pabla, S., Glenn, S. T., Seager, R. J., Roey, E. V., Gao, S., Burgher, B., Andreas, J., Giamo, V., Mallon, M., et al. (2021) · PLoS ONE · doi:10.1371/journal.pone.0260089 · Cited by 52
Translating the evolving molecular landscape of tumors to biomarkers of response for cancer immunotherapy
Anagnostou, V., Landon, B. V., Medina, J. E., Forde, P. M., & Velculescu, V. E. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abo3958 · Cited by 52
Tumor mutation burden in the prognosis and response of lung cancer patients to immune-checkpoint inhibition therapies
Vryza, P., Fischer, T., Mistakidi, E., & Zaravinos, A. (2023) · Translational Oncology · doi:10.1016/j.tranon.2023.101788 · Cited by 55
Dendritic cell-targeted therapy expands CD8 T cell responses to bona-fide neoantigens in lung tumors
López, L., Morosi, L. G., Terza, F. L., Bourdely, P., Rospo, G., Amadio, R., Piperno, G. M., Russo, V., Volponi, C., Vodret, S., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-46685-y · Cited by 55
Blood-based biomarkers in patients with non-small cell lung cancer treated with immune checkpoint blockade
Tsai, Y.-T., Schlom, J., & Donahue, R. N. (2024) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-024-02969-1 · Cited by 56
High tumor mutation burden is associated with DNA damage repair gene mutation in breast carcinomas
Mei, P., Freitag, C. E., Wei, L., Zhang, Y., Parwani, A. V., & Li, Z. (2020) · Diagnostic Pathology · doi:10.1186/s13000-020-00971-7 · Cited by 55
Current status and future potential of predictive biomarkers for immune checkpoint inhibitors in gastric cancer
Kang, B. W., & Chau, I. (2020) · ESMO Open · doi:10.1136/esmoopen-2020-000791 · Cited by 50
Immunotherapy as Single Treatment for Patients With NSCLC With Brain Metastases: A Systematic Review and Meta-Analysis—the META-L-BRAIN Study
de Alencar, V. T. L., Camandaroba, M. P. G., Pirolli, R., Fogassa, C. A. Z., & de Lima, V. C. C. (2021) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2021.04.014 · Cited by 53
Paired whole exome and transcriptome analyses for the Immunogenomic changes during concurrent chemoradiotherapy in esophageal squamous cell carcinoma
Park, S., Joung, J., Min, Y. W., Nam, J., Ryu, D., Oh, D., Park, W., Lee, S. K., Choi, Y., Ahn, J. S., et al. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0609-x · Cited by 53
PD-L1 Expression Is Significantly Associated with Tumor Mutation Burden and Microsatellite Instability Score
Cho, Y. A., Lee, H., Kim, D. G., Kim, H., Ha, S. Y., Choi, Y., Jang, K., & Kim, K. (2021) · Cancers · doi:10.3390/cancers13184659 · Cited by 52
Anti-PD-L1 F(ab) Conjugated PEG-PLGA Nanoparticle Enhances Immune Checkpoint Therapy
Lee, C. K., Atibalentja, D. F., Yao, L. E., Park, J., Kuruvilla, S. P., & Felsher, D. W. (2022) · Nanotheranostics · doi:10.7150/ntno.65544 · Cited by 55
On-treatment blood TMB as predictors for camrelizumab plus chemotherapy in advanced lung squamous cell carcinoma: biomarker analysis of a phase III trial
Jiang, T., Chen, J., Xu, X., Cheng, Y., Chen, G., Pan, Y., Fang, Y., Wang, Q., Huang, Y., Yao, W., et al. (2022) · Molecular Cancer · doi:10.1186/s12943-021-01479-4 · Cited by 50
Deciphering radiological stable disease to immune checkpoint inhibitors
Luo, J., Wu, S., Rizvi, H. A., Zhang, Q., Egger, J. V., Osorio, J. C., Schoenfeld, A. J., Plodkowski, A. J., Ginsberg, M. S., Callahan, M. K., et al. (2022) · Annals of Oncology · doi:10.1016/j.annonc.2022.04.450 · Cited by 52
Self-citation
Molecular diagnostics tailoring personalized cancer therapy—an oncologist’s view
Riedl, J. M., Moik, F., Esterl, T., Kostmann, S. M., Gerger, A., & Jost, P. J. (2023) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-023-03702-7 · Cited by 62
Treatment of NSCLC after chemoimmunotherapy — are we making headway?
Reck, M., Frost, N., Peters, S., Fox, B. A., Ferrara, R., Savai, R., & Barlési, F. (2025) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-025-01061-7 · Cited by 62
Self-citation
Combination of PD-1/PD-L1 and CTLA-4 inhibitors in the treatment of cancer – a brief update
Park, J., & Skålhegg, B. S. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1680838 · Cited by 66
CXCR4 Based Therapeutics for Non-Small Cell Lung Cancer (NSCLC)
Wald, O. (2018) · Journal of Clinical Medicine · doi:10.3390/jcm7100303 · Cited by 52
Mechanisms of Primary and Secondary Resistance to Immune Checkpoint Inhibitors in Cancer
Seto, T., Sam, D. L., & Pan, M. (2019) · Medical Sciences · doi:10.3390/medsci7020014 · Cited by 52
Strategies to Augment Natural Killer (NK) Cell Activity against Solid Tumors
Chen, Z., Yang, Y., Liu, L. L., & Lundqvist, A. (2019) · Cancers · doi:10.3390/cancers11071040 · Cited by 53
Probody Therapeutic Design of 89Zr-CX-072 Promotes Accumulation in PD-L1–Expressing Tumors Compared to Normal Murine Lymphoid Tissue
Giesen, D., Broer, L. N., Hooge, M. N. L., Popova, I., Howng, B., Nguyen, M. T. L., Vasiljeva, O. S., de Vries, E. G. E., & Pool, M. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-3137 · Cited by 52
Tumor-Derived IL33 Promotes Tissue-Resident CD8+ T Cells and Is Required for Checkpoint Blockade Tumor Immunotherapy
Chen, L., Sun, R., Xu, J., Zhai, W., Zhang, D., Yang, M., Yue, C., Chen, Y., Li, S., Turnquist, H. R., et al. (2020) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-19-1024 · Cited by 52
Identification and Utilization of Biomarkers to Predict Response to Immune Checkpoint Inhibitors
Gjoerup, O. V., Brown, C. A., Ross, J. S., Huang, R. S. P., Schrock, A. B., Creeden, J., Fabrizio, D. A., & Tolba, K. A. (2020) · The AAPS Journal · doi:10.1208/s12248-020-00514-4 · Cited by 52
Tumor Mutational Burden in Breast Cancer: Current Evidence, Challenges, and Opportunities
Barroso‐Sousa, R., Pacifico, J. P. M., Sammons, S. L., & Tolaney, S. M. (2023) · Cancers · doi:10.3390/cancers15153997 · Cited by 54
Immunotherapy-related biomarkers: Confirmations and uncertainties
Catalano, M., Iannone, L. F., Nesi, G., Nobili, S., Mini, E., & Roviello, G. (2023) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2023.104135 · Cited by 61
Hyperspectral cell sociology reveals spatial tumor-immune cell interactions associated with lung cancer recurrence
Enfield, K. S. S., Martin, S. D., Marshall, E. A., Kung, S. H. Y., Gallagher, P., Milne, K., Chen, Z., Nelson, B. H., Lam, S. C., English, J. C., et al. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-018-0488-6 · Cited by 51
Phase I Trial of Targeted EGFR or ALK Therapy with Ipilimumab in Metastatic NSCLC with Long-Term Follow-Up
Chalmers, A. W., Patel, S. B., Boucher, K. M., Cannon, L. A., Esplin, M., Luckart, J. B., Graves, N., Duren, T. V., & Akerley, W. (2019) · Targeted Oncology · doi:10.1007/s11523-019-00658-0 · Cited by 50
T-Cell Immunotherapies Targeting Histocompatibility and Tumor Antigens in Hematological Malignancies
Janelle, V., Rulleau, C., Testa, S. D., Carli, C., & Delisle, J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00276 · Cited by 52
Immune Therapy Opportunities in Ovarian Cancer
Kandalaft, L. E., Odunsi, K. O., & Coukos, G. (2020) · American Society of Clinical Oncology Educational Book · doi:10.1200/edbk_280539 · Cited by 52
Impact of cancer cachexia on the therapeutic outcome of combined chemoimmunotherapy in patients with non-small cell lung cancer: a retrospective study
Morimoto, K., Uchino, J., Yokoi, T., Kijima, T., Gotô, Y., Nakao, A., Hibino, M., Takeda, T., Yamaguchi, H., Takumi, C., et al. (2021) · OncoImmunology · doi:10.1080/2162402x.2021.1950411 · Cited by 49
Intratumor Heterogeneity and Antitumor Immunity Shape One Another Bidirectionally
Wolf, Y., & Samuels, Y. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-1355 · Cited by 51
Development and Validation of a DNA Methylation-related Classifier of Circulating Tumour Cells to Predict Prognosis and to provide a therapeutic strategy in Lung Adenocarcinoma
Gu, X., Huang, X., Zhang, X., & Wang, C. (2022) · International Journal of Biological Sciences · doi:10.7150/ijbs.75284 · Cited by 50
Prognostic value of inflammatory and nutritional indexes among advanced NSCLC patients receiving PD ‐1 inhibitor therapy
Fang, Q., Yu, J., Li, W., Luo, J., Deng, Q., Chen, B., He, Y., Zhang, J., & Zhou, C. (2022) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.13740 · Cited by 49
CHI3L1 enhances melanoma lung metastasis via regulation of T cell co-stimulators and CTLA-4/B7 axis
Ma, B., Kamle, S., Akosman, B., Khan, H., Lee, C.-M., Lee, C. G., & Elias, J. A. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1056397 · Cited by 47
Immunotherapy for oncogenic-driven advanced non-small cell lung cancers: Is the time ripe for a change?
Remón, J., Hendriks, L. E. L., Cabrera, C., Reguart, N., & Besse, B. (2018) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2018.10.006 · Cited by 49
Precision oncology: separating the wheat from the chaff
Remón, J., & Dienstmann, R. (2018) · ESMO Open · doi:10.1136/esmoopen-2018-000446 · Cited by 49
T cell-inflamed phenotype and increased Foxp3 expression in infiltrating T-cells of mismatch-repair deficient endometrial cancers
Asaka, S., Yen, T., Wang, T., Shih, I., & Gaillard, S. L. (2018) · Modern Pathology · doi:10.1038/s41379-018-0172-x · Cited by 49
Clinical and Immunological Implications of Frameshift Mutations in Lung Cancer
Chae, Y. K., de Viveiros, P. A. H., Junior, G. L. L., Sukhadia, B., Sheikh, M. M., Saravia, D., Florou, V., Sokol, E. S., Frampton, G. M., Chalmers, Z. R., et al. (2019) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2019.06.016 · Cited by 48
Identification of Recurrent Activating HER2 Mutations in Primary Canine Pulmonary Adenocarcinoma
Lorch, G., Sivaprakasam, K., Zismann, V., Perdigones, N., Contente‐Cuomo, T., Nazareno, A., Facista, S. J., Wong, S., Drenner, K., Liang, W. S., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-1145 · Cited by 49
Novel Biomarkers for Personalized Cancer Immunotherapy
Shindo, Y., Hazama, S., Tsunedomi, R., Suzuki, N., & Nagano, H. (2019) · Cancers · doi:10.3390/cancers11091223 · Cited by 49
Tumour mutational burden: primary versus metastatic tissue creates systematic bias
Schnidrig, D., Turajlic, S., & Litchfield, K. (2019) · Immuno-Oncology Technology · doi:10.1016/j.iotech.2019.11.003 · Cited by 48

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: Hellmann, Matthew D.
Ciuleanu, Tudor-Eliade
Lee, Jong Seok
Otterson, Gregory A.
Audigier-Valette, Clarisse
Linardou, Helena
Burgers, Sjaak
Salman, Pamela
Borghaei, Hossein
Ramalingam, Suresh S.
Brahmer, Julie
Reck, Martin
Geese, William J.
Green, George
Szustakowski, Joseph
Fu, Yali
Paz-Ares, Luis
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: bronze
doi.org
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

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

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks