The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial
Abstract
Background Patients with recurrent or metastatic squamous cell carcinoma of the head and neck have few treatment options. We aimed to assess the safety, tolerability, and antitumour activity of pembrolizumab, a humanised anti-programmed death receptor 1 (PD-1) antibody, in patients with PD-L1-positive recurrent or metastatic squamous cell carcinoma of the head and neck. Methods This study was an open-label, multicentre, phase 1b trial of patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Patients were eligible for enrolment if they were aged 18 years or older, had a confirmed diagnosis of recurrent or metastatic squamous cell carcinoma of the head and neck, and had any level of PD-L1 expression (ie, at least 1% of tumour cells or stroma that were PD-L1-positive by immunohistochemistry). Patients received pembrolizumab 10 mg/kg intravenously every 2 weeks. Primary outcomes were safety in the per-protocol population and the proportion of patients with centrally reviewed overall response per Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1). Overall response was analysed in the full analysis set, which was defined as all patients who had received at least one dose of pembrolizumab, had measurable disease at baseline, and one post-baseline scan or patients without a post-baseline scan who discontinued therapy because of disease progression or a drug-related adverse event. The study is registered with ClinicalTrials.gov, number NCT…
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“These findings highlight virus-specific T cells in anti-tumor responses during ICB.”
From Contrasting cytotoxic and regulatory T cell responses underlying distinct clinical outcomes to anti-PD-1 plus lenvatinib therapy in cancer (2025) · cites this paper as [78]
In the citing paper
“Clinical studies show enhanced responses to PD-1 blockade in HNSCC patients with human papillomavirus infection compared to those without.78”
From Contrasting cytotoxic and regulatory T cell responses underlying distinct clinical outcomes to anti-PD-1 plus lenvatinib therapy in cancer (2025) · cites this paper as [78]
Citations
Cites
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838
Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200690 · Cited by 12,628
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 for the Treatment of Non–Small-Cell Lung Cancer
Garon, E. B., Rizvi, N. A., Hui, R., Leighl, N., Balmanoukian, A. S., Eder, J. P., Patnaik, A., Aggarwal, C., Gubens, M., Horn, L., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1501824 · Cited by 6,198
Self-citationPD-1 and Its Ligands in Tolerance and Immunity
Keir, M. E., Butte, M. J., Freeman, G. J., & Sharpe, A. H. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090331 · Cited by 5,378
Freeman, G. J., Long, A. J., Iwai, Y., Bourque, K., Chernova, T., Nishimura, H., Fitz, L. J., Malenkovich, N., Okazaki, T., Byrne, M. C., et al. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.7.1027 · Cited by 5,294
Comprehensive genomic characterization of head and neck squamous cell carcinomas
The Cancer Genome Atlas Network (2015) · Nature · doi:10.1038/nature14129 · Cited by 4,147
Platinum-Based Chemotherapy plus Cetuximab in Head and Neck Cancer
Vermorken, J. B., Mesia, R., Rivera, F., Remenar, E., Kawecki, A., Rottey, S., Erfan, J., Zabolotnyy, D., Kienzer, H.-R., Cupissol, D., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802656 · Cited by 3,726
Safety and Tumor Responses with Lambrolizumab (Anti–PD-1) in Melanoma
Hamid, O., Robert, C., DAUD, A. I., Hodi, F. S., Hwu, W., Kefford, R. F., Wolchok, J. D., Hersey, P., Joseph, R. W., Weber, J. S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1305133 · Cited by 3,427
PD-L2 is a second ligand for PD-1 and inhibits T cell activation
Latchman, Y., Wood, C. R., Chernova, T., Chaudhary, D., Borde, M., Chernova, I., Iwai, Y., Long, A. J., Brown, J. A., Nunes, R., et al. (2001) · Nature Immunology · doi:10.1038/85330 · Cited by 2,955
Research works printed but not linked: 1
- Burtness, 2015, Moving forward in the management of squamous cell carcinoma of the head and neck: promising immuno-oncology approaches, Am J Hematol Oncol, 11, 28
Cited by
Sorted by citations
Items 201–300 of 1,001
de la Iglesia, J. V., Slebos, R. J. C., Martin‐Gomez, L., Wang, X., Teer, J. K., Tan, A. C., Gerke, T. A., Aden-Buie, G., van Veen, T., Masannat, J., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-1769 · Cited by 120
Li, Z., Zheng, Z., Wei, Z.-H., Zhang, L., Li, F., Lin, L., Liu, R., Huang, X., Lv, J., Chen, F., et al. (2019) · Theranostics · doi:10.7150/thno.36585 · Cited by 114
“Recent studies have shown promising outcomes with anti-programmed cell death (PD)-1 therapy in advanced HNSC, although these agents benefit only a subset of patients [4-6].”
BackgroundFoy, J., Bertolus, C., Michallet, M., Deneuve, S., Incitti, R., Bendriss‐Vermare, N., Albaret, M. A., Ortiz‐Cuaran, S., Thomas, E., Colombe, A., et al. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx210 · Cited by 94
“HPV-positive HNSCC harbor fewer mutations [28] and present a higher response to anti-PD1 when compared with HPV-negative HNSCC [14, 15, 29].”
InfluentialTahara, M., Kiyota, N., Yokota, T., Hasegawa, Y., Muro, K., Takahashi, S., Onoe, T., Homma, A., Taguchi, J., Suzuki, M., et al. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy040 · Cited by 89
“Recently, immune checkpoint inhibitors such as anti-PD-1/ PDL-1 antibody have demonstrated promising efficacy [15, 16].”
BackgroundFriedman, J., Moore, E. C., Zolkind, P., Robbins, Y., Clavijo, P. E., Sun, L., Greene, S., Morisada, M. V., Mydlarz, W. K., Schmitt, N., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-2209 · Cited by 88
“org Clin Cancer Res; 26(3) February 1, 2020 683”
BackgroundInfluentialEnhancing clinical and immunological effects of anti-PD-1 with belapectin, a galectin-3 inhibitor
Curti, B. D., Koguchi, Y., Leidner, R. S., Rolig, A. S., Sturgill, E. R., Sun, Z., Wu, Y., Rajamanickam, V., Bernard, B. M., Hilgart-Martiszus, I., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-002371 · Cited by 104
“The primary objective of the trial was to determine a safe dose of GR-MD-02 used in combination with pembroli-zumab 200 mg IV every 3 weeks.”
Zhang, L., Li, B., Yu, P., Wu, F., Li, Q., Lin, Z., Xie, S., Xiao, L., Lin, X., Ou, Z., et al. (2020) · Oral Oncology · doi:10.1016/j.oraloncology.2020.104943 · Cited by 93
Role of Tumor-Mediated Dendritic Cell Tolerization in Immune Evasion
DeVito, N. C., Plebanek, M. P., Theivanthiran, B., & Hanks, B. A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02876 · Cited by 105
Pembrolizumab in cervical cancer: latest evidence and clinical usefulness
Borcoman, É., & Tourneau, C. L. (2017) · Therapeutic Advances in Medical Oncology · doi:10.1177/1758834017708742 · Cited by 89
Shen, D., Chen, Q., Wu, J., Li, J., Tao, K., & Jiang, Y. (2021) · Journal of Gastrointestinal Oncology · doi:10.21037/jgo-20-599 · Cited by 95
“However, with the good effect of immune checkpoint inhibitors (ICIs) being observed in many kinds of cancer, including melanoma (18), head and neck squamous cell cancer (19), non-small cell lung cancer (20), renal cell cancer (21), urothelial cancer (22), and relapsed or refractory Hodgkin’s lymphoma (23), further exp…”
BackgroundHuang, W., Zhang, L., Yang, M. Y., Wu, X., Wang, X., Huang, W., Lu, Y., Pan, H., Wang, Y., Wang, Z., et al. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-01878-x · Cited by 105
Clavijo, P. E., Moore, E., Chen, J.-H., Davis, R. J., Friedman, J., Kim, Y., Waes, C. V., Chen, Z., & Allen, C. (2017) · OncoTarget · doi:10.18632/oncotarget.18437 · Cited by 87
“Objective responses to checkpoint inhibition tend to be durable, but only a small subset of patients respond [5].”
Paraghamian, S. E., Longoria, T. C., & Eskander, R. N. (2017) · Gynecologic Oncology Research and Practice · doi:10.1186/s40661-017-0038-9 · Cited by 94
“In KEYNOTE-012, a phase Ib trial of pembrolizumab 10 mg per kg every 2 weeks in patients with PD-L1-positive recurrent or metastatic HNSCC, overall response rate (ORR) in all patients was 18% (8 of 45 patients), which consisted of 4 of 29 (14%) patients with HPV-negative tumors and 4 of 16 (25%) patients with HPV-posi…”
BackgroundKujan, O., van Schaijik, B., & Farah, C. S. (2020) · Cancers · doi:10.3390/cancers12071937 · Cited by 99
“2016 [41] Low Moderate Moderate High Moderate Low”
BackgroundInfluentialMaruse, Y., Kawano, S., Jinno, T., Matsubara, R., Goto, Y., Kaneko, N., Sakamoto, T., Hashiguchi, Y., Moriyama, M., Toyoshima, T., et al. (2018) · International Journal of Oral and Maxillofacial Surgery · doi:10.1016/j.ijom.2018.01.004 · Cited by 86
NSD1 inactivation defines an immune cold, DNA hypomethylated subtype in squamous cell carcinoma
Brennan, K., Shin, J. H., Tay, J. K., Prunello, M., Gentles, A. J., Sunwoo, J. B., & Gevaert, O. (2017) · Scientific Reports · doi:10.1038/s41598-017-17298-x · Cited by 94
Adam, J., Louvet, E., Sourisseau, T., Dorvault, N., Bernard, M., Maingot, E., Faivre, L., Kuo, M.-S., Boissier, É., Dessoliers, M.-C., et al. (2018) · ESMO Open · doi:10.1136/esmoopen-2017-000257 · Cited by 96
“With the exception of the constitutional high-level microsatellite instability status,(29) PD-L1 expression remains the most robust predictive biomarker for response to anti-PD-1/PD-L1 therapy in various tumour types.(17) Our anti-PD-L1 clone, staining and scoring method used had been previously validated and displaye…”
ResultBrooks, J. M., de Menezes, A. N., Ibrahim, M., Archer, L., Lal, N., Bagnall, C. J., von Zeidler, S. V., Valentine, H. R., Spruce, R. J., Batis, N., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-3314 · Cited by 110
“More recently, evidence has emerged for the efficacy of immune checkpoint inhibitors in HNC (19, 20).”
BackgroundInfluentialSelf-citationChang, X., Lu, X., Guo, J., & Teng, G. (2018) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2018.08.006 · Cited by 86
Systematic Review of PD-1/PD-L1 Inhibitors in Oncology: From Personalized Medicine to Public Health
Chang, E., Pelosof, L. C., Lemery, S. J., Gong, Y. U. T., Goldberg, K. B., Farrell, A. T., Keegan, P., Veeraraghavan, J., Wei, G., Blumenthal, G. M., et al. (2021) · The Oncologist · doi:10.1002/onco.13887 · Cited by 94
Ahern, E. S., Harjunpää, H., O’Donnell, J. S., Allen, S. M., Dougall, W. C., Teng, M. W. L., & Smyth, M. J. (2018) · OncoImmunology · doi:10.1080/2162402x.2018.1431088 · Cited by 93
“Antibodies targeting the immune checkpoint receptor programmed death-1 (PD1) are indicated in the treatment of several malignancies.(1,2,3,4,5) Importantly, studies in melanoma in”
BackgroundKobayashi, Y., Lim, S., & Yamaguchi, H. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.11.011 · Cited by 96
Radioimmunotherapy for the treatment of head and neck cancer
Karam, S. D., & Raben, D. (2019) · The Lancet Oncology · doi:10.1016/s1470-2045(19)30306-7 · Cited by 104
Ock, C.-Y., Kim, S., Keam, B., Kim, S., Ahn, Y., Chung, E., Kim, J.-H., Kim, T. M., Kwon, S. K., Jeon, Y. K., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.18542 · Cited by 90
“com/oncotarget of tumor-infiltrating lymphocytes [5, 6], and interferongamma signature [7] have been suggested for predicting the response to anti-PD-1/PD-L1 inhibitors; among these, PD-L1 expression in tumor cells is a promising and simple predictive biomarker [8, 9].”
BackgroundInflammatory Arthritis: A Newly Recognized Adverse Event of Immune Checkpoint Blockade
Naidoo, J., Cappelli, L. C., Forde, P. M., Marrone, K. A., Lipson, E. J., Hammers, H. J., Sharfman, W. H., Le, D. T., Baer, A. N., Shah, A. A., et al. (2017) · The Oncologist · doi:10.1634/theoncologist.2016-0390 · Cited by 81
“[7, 8, 12]; pembrolizumab for head and neck squamous carcinoma [13]; and atezolizumab for urothelial carcinoma [9].”
BackgroundPatel, J. J., Levy, D. A., Nguyen, S. A., Knochelmann, H. M., & Day, T. A. (2019) · Head & Neck · doi:10.1002/hed.26036 · Cited by 83
“Bauml (2017) 171 108 (63) 100 NA NA NA 1 (1) 28 (16) 30 (18) 0”
Mutational and Antigenic Landscape in Tumor Progression and Cancer Immunotherapy
Vitale, I., Sistigu, A., Manic, G., Rudqvist, N.-P., Trajanoski, Z., & Galluzzi, L. (2019) · Trends in Cell Biology · doi:10.1016/j.tcb.2019.01.003 · Cited by 95
Immune Evasion by Head and Neck Cancer: Foundations for Combination Therapy
Horton, J. D., Knochelmann, H. M., Day, T. A., Paulos, C. M., & Neskey, D. M. (2019) · Trends in cancer · doi:10.1016/j.trecan.2019.02.007 · Cited by 93
“Keynote-012 was an open-label, multicenter, Phase Ib trial of pembrolizumab for r/m HNSCC [43] that demonstrated an overall response rate of 18% (25% in HPV+ and 14% in HPV–).”
BackgroundHuang, Y., Sun, J., Li, J., Zhu, D., Dong, M., Dou, S., Tang, Y., Shi, W., Sun, Q., Zhao, T., et al. (2022) · International Journal of Surgery · doi:10.1097/js9.0000000000000489 · Cited by 99
“This led to the 2019 approval of pembrolizumab as first-line therapy in patients with HNSCC whose tumors had CPS greater than or equal to 1([13,35]).”
Bridge, J. A., Lee, J., DAUD, A. I., Wells, J. W., & Bluestone, J. A. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00351 · Cited by 86
Hong, D., Moore, K., Patel, M., Grant, S., Burris, H., William, W., Jones, S., Meric-Bernstam, F., Infante, J., Golden, L., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-3347 · Cited by 79
“Historically, response rates for patients with previously treatedmetastatic disease have been less than 15%, but PD-1 and PD-L1 inhibitors have recently demonstrated response rates of up to 18% (29, 30).”
BackgroundYang, Z., Yan, G., Zheng, L., Gu, W., Liu, F., Chen, W., Cui, X., Wang, Y., Yang, Y., Chen, X., et al. (2021) · OncoImmunology · doi:10.1080/2162402x.2021.1938890 · Cited by 105
“In 2016, the anti-PD-1 antibodies pembrolizumab and nivolumab were approved by the FDA to treat metastatic and recurrent HNSCC.(5,6) However, the objective response rate to and survival benefit from ICBs remain low,(7) and OSCC generally has the lowest immune cell infiltration level in HNSCC.”
BackgroundInfluentialA good start of immunotherapy in esophageal cancer
Zhao, Q., Yu, J., & Meng, X. (2019) · Cancer Medicine · doi:10.1002/cam4.2336 · Cited by 86
Tang, T., Abu‐Sbeih, H., Luo, W., Lum, P. J., Qiao, W., Bresalier, R. S., Richards, D. M., & Wang, Y. (2019) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365521.2019.1594356 · Cited by 85
Evolution of Cancer Vaccines—Challenges, Achievements, and Future Directions
Tay, B. Q., Wright, Q., Ladwa, R., Perry, C., Leggatt, G., Simpson, F., Wells, J. W., Panizza, B. J., Frazer, I. H., & Cruz, J. L. G. (2021) · Vaccines · doi:10.3390/vaccines9050535 · Cited by 76
Foster, C. C., Couey, M., Kochanny, S. E., Khattri, A., Acharya, R. K., Tan, Y. C., Brisson, R. J., Leidner, R. S., & Seiwert, T. Y. (2021) · Cancer · doi:10.1002/cncr.33780 · Cited by 83
Self-citationLechien, J., Descamps, G., Seminerio, I., Furgiuele, S., Dequanter, D., Mouawad, F., Badoual, C., Journé, F., & Saussez, S. (2020) · Cancers · doi:10.3390/cancers12051060 · Cited by 76
“demonstrated that p16+ patients treated with Nivolumab had significantly the highest survivals compared to p16− ones [166,175,176].”
BackgroundGuo, L., Wei, R., Lin, Y., & Kwok, H. F. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01508 · Cited by 85
“Recurrent or metastatic HNSCC NCT01848834 (70) Ib First line”
BackgroundImmune Checkpoint Inhibitor-Induced Colitis: Diagnosis and Management
Prieux‐Klotz, C., Dior, M., Damotte, D., Dréanic, J., Brieau, B., Brézault, C., Abitbol, V., Chaussade, S., & Coriat, R. (2017) · Targeted Oncology · doi:10.1007/s11523-017-0495-4 · Cited by 76
“Additional indications, including urothelial cancer [16–18], head and neck squamous cell carcinoma [19, 20], gastric cancer [21], mismatch-repair deficient colorectal cancer [22], ovarian cancer [23], Merkel cell carcinoma [24], and Hodgkin lymphoma [25] are under regulatory consideration.”
BackgroundImmunotherapy With Radiotherapy and Chemoradiotherapy for Cervical Cancer
Feng, C. H., Mell, L. K., Sharabi, A. B., McHale, M. T., & Mayadev, J. (2020) · Seminars in Radiation Oncology · doi:10.1016/j.semradonc.2020.05.003 · Cited by 86
Song, P., Zhang, D., Cui, X., & Zhang, L. (2020) · Thoracic Cancer · doi:10.1111/1759-7714.13541 · Cited by 84
Targeting cancer stem cells in squamous cell carcinoma
Chen, D., & Wang, C. (2019) · Precision Clinical Medicine · doi:10.1093/pcmedi/pbz016 · Cited by 83
“In these pilot studies, results have demonstrated that nivolumab and pembrolizumab can improve overall survival of HNSCC compared with traditional chemotherapy.(4,165,166) However, response rates to nivolumab and pembrolizumab in HNSCC remain low, ranging only from 13% to 20%, whereas survival has improved in one of 1…”
ResultLiu, L.-H., Lim, M., Jung, S.-N., Oh, C., Won, H.-R., Jin, Y.-L., Piao, Y.-D., Kim, H. J., Chang, J., & Koo, B. (2021) · Phytomedicine · doi:10.21203/rs.3.rs-431391/v1 · Cited by 73
Yu, Y., & Lee, N. Y. (2018) · Future Oncology · doi:10.2217/fon-2018-0405 · Cited by 91
Immunotherapy in head and neck cancer: aiming at EXTREME precision
Szturz, P., & Vermorken, J. B. (2017) · BMC Medicine · doi:10.1186/s12916-017-0879-4 · Cited by 73
“Altogether, both KEYNOTE-012 cohorts [32, 33] contained a substantial proportion of heavily pre-treated participants, median age ranged between 60 and 63 years, and most of the responding patients had an ongoing response at the time of data cut-off.”
BackgroundAmeratunga, M., Chénard-Poirier, M., Candilejo, I. M., Pedregal, M., Lui, A., Dolling, D. I., Aversa, C., Garces, A. I., Ang, J. E., Banerji, U., et al. (2017) · European Journal of Cancer · doi:10.1016/j.ejca.2017.11.012 · Cited by 76
Trial watch: immune checkpoint blockers for cancer therapy
Vanpouille-Box, C., Lhuillier, C., Bezu, L., Aranda, F., Yamazaki, T., Kepp, O., Fucikova, J., Spisek, R., Demaria, S., Formenti, S. C., et al. (2017) · OncoImmunology · doi:10.1080/2162402x.2017.1373237 · Cited by 73
Paolino, G., Pantanowitz, L., Barresi, V., Pagni, F., Munari, E., Moretta, L., Brunelli, M., Bariani, E., Vigliar, E., Pisapia, P., et al. (2021) · Pathology - Research and Practice · doi:10.1016/j.prp.2021.153605 · Cited by 76
Update on oral and oropharyngeal cancer staging – International perspectives
Kato, M. G., Baek, C., Chaturvedi, P., Gallagher, R., Kowalski, L. P., Leemans, C., Warnakulasuriya, S., Nguyen, S. A., & Day, T. (2020) · World Journal of Otorhinolaryngology-Head and Neck Surgery · doi:10.1016/j.wjorl.2019.06.001 · Cited by 72
PD-L1: a novel prognostic biomarker in head and neck squamous cell carcinoma
Müller, T., Braun, M., Dietrich, D., Aktekin, S., Höft, S., Kristiansen, G., Göke, F., Schröck, A., Brägelmann, J., Held, S. A. E., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.17547 · Cited by 119
“Perhaps, treatment-related acute and late toxicity of conventional radiochemotherapy could be reduced by complementary therapies targeting the PD-1/PD-L1 pathway in the future [17, 18, 32].”
BackgroundInfluentialWang, Y., Ma, R., Liu, F., Lee, S. A., & Zhang, L. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00374 · Cited by 71
HPV Detection in Head and Neck Squamous Cell Carcinomas: What Is the Issue?
Augustin, J., Lépine, C., Morini, A., Brunet, A., Veyer, D., Brochard, C., Mirghani, H., Péré, H., & Badoual, C. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.01751 · Cited by 71
MAPK Signaling Pathway in Oral Squamous Cell Carcinoma: Biological Function and Targeted Therapy
Cheng, Y., Chen, J., Shi, Y., Fang, X., & Tang, Z. (2022) · Cancers · doi:10.3390/cancers14194625 · Cited by 85
Nassar, A. H., Mouw, K. W., Jegede, O. A., Shinagare, A. B., Kim, J., Liu, C., Pomerantz, M. M., Harshman, L. C., Allen, E. M. V., Wei, X. X., et al. (2019) · British Journal of Cancer · doi:10.1038/s41416-019-0686-0 · Cited by 74
Management of recurrent and metastatic oral cavity cancer: Raising the bar a step higher
Szturz, P., & Vermorken, J. B. (2019) · Oral Oncology · doi:10.1016/j.oraloncology.2019.104492 · Cited by 79
Immune Response Against Head and Neck Cancer: Biological Mechanisms and Implication on Therapy
Perri, F., Ionna, F., Longo, F., Scarpati, G. D. V., Angelis, C. D., Ottaiano, A., Botti, G., & Caponigro, F. (2019) · Translational Oncology · doi:10.1016/j.tranon.2019.11.008 · Cited by 73
Tam, S., Yao, C., Amit, M., Gajera, M. V., Luo, X., Treistman, R., Khanna, A., Aashiq, M., Nagarajan, P., Bell, D., et al. (2019) · JAMA Otolaryngology - Head and Neck Surgery · doi:10.1001/jamaoto.2019.3751 · Cited by 69
Emerging therapies for breast cancer
Hu, X., Huang, W., & Fan, M. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0466-3 · Cited by 71
“Pembrolizumab is approved in several countries for the treatment of advanced melanoma [76], non-small cell lung cancer in certain situations [77], and as a second-line treatment for head and neck squamous cell carcinoma [78].”
BackgroundGalvis, M. M., Borges, G. Á., de Oliveira, T. B., de Toledo, I. P., CASTILHO, R. M., Guerra, E. N. S., Kowalski, L. P., & SQUARIZE, C. H. (2020) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2020.102966 · Cited by 88
Guidi, A., Codecà, C., & Ferrari, D. (2018) · Medical Oncology · doi:10.1007/s12032-018-1096-5 · Cited by 68
Radiotherapy and Immunotherapy for Head and Neck Cancer: Current Evidence and Challenges
Qian, J. M., & Schoenfeld, J. D. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2020.608772 · Cited by 84
Hyperthermia and immunotherapy: clinical opportunities
Hurwitz, M. (2019) · International Journal of Hyperthermia · doi:10.1080/02656736.2019.1653499 · Cited by 67
New Therapies in Head and Neck Cancer
Santuray, R. T., Johnson, D. E., & Grandis, J. R. (2018) · Trends in cancer · doi:10.1016/j.trecan.2018.03.006 · Cited by 67
“Moreover, median duration of response (time from initial disease response to disease progression) for pembrolizumab was 53 weeks compared to 4 months for cetuximab [54].”
BackgroundOuth-Gauer, S., Alt, M., Tourneau, C. L., Augustin, J., Broudin, C., Gasne, C., Denize, T., Mirghani, H., Fabre, E., Ménard, M., et al. (2018) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2018.02.008 · Cited by 73
Role of Immunotherapy in Head and Neck Cancer
Ling, D. C., Bakkenist, C. J., Ferris, R. L., & Clump, D. A. (2017) · Seminars in Radiation Oncology · doi:10.1016/j.semradonc.2017.08.009 · Cited by 75
mTOR Signalling in Head and Neck Cancer: Heads Up
Tan, F. H., Bai, Y., Saintigny, P., & Darido, C. (2019) · Cells · doi:10.3390/cells8040333 · Cited by 69
Economopoulou, P., Kotsantis, I., & Psyrri, A. K. (2016) · ESMO Open · doi:10.1136/esmoopen-2016-000122 · Cited by 63
Tumor microenvironment and immune-related therapies of head and neck squamous cell carcinoma
Qin, Y., Zheng, X., Gao, W., Wang, B., & Wu, Y. (2021) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2021.01.011 · Cited by 76
Borel, C., Jung, A. C., & Burgy, M. (2020) · Cancers · doi:10.3390/cancers12092691 · Cited by 78
“Above all, most of these responses were durable with a median of 53 weeks, a median PFS of 2 months (95% CI: 2–4) and a particularly interesting median survival of 13 months (95% CI: 5 – not reached) [6].”
BackgroundInfluentialBigelow, E. O., Seiwert, T., & Fakhry, C. (2020) · Oral Oncology · doi:10.1016/j.oraloncology.2020.104652 · Cited by 65
Self-citationExpression of PD-1/PD-L1 in head and neck squamous cell carcinoma and its clinical significance
Chen, S.-W., Li, S.-M., Shi, D., Jiang, W.-M., Song, M., Yang, A., Li, Y.-D., Bei, J.-X., Chen, W.-K., & Zhang, Q. (2019) · International Journal of Biological Markers · doi:10.1177/1724600819884722 · Cited by 64
Immune profiles in primary squamous cell carcinoma of the head and neck
Saloura, V., Izumchenko, E., Zuo, Z., Bao, R., Korzinkin, M., Ozerov, I. V., Zhavoronkov, A. A., Sidransky, D., Bedi, A., Hoque, M. O., et al. (2019) · Oral Oncology · doi:10.1016/j.oraloncology.2019.06.032 · Cited by 73
“PD-L1 staining was performed using the SP142 antibody (Ventana) and its expression was evaluated on tumor cells (TC), as well as tumor-infiltrating immune cells (IC) as previously described [3, 16].”
BackgroundMethodSelf-citationdu Rusquec, P., de Calbiac, O., Robert, M., Campone, M., & Frenel, J. (2019) · Cancer Management and Research · doi:10.2147/cmar.s151023 · Cited by 77
“Tumor inflammation composite scores have been evaluated and indicate that the efficacy of pembrolizumab is correlated to a high density of immune cells.(34,98,99) Different strategies aiming at increasing infiltration of immune cell in tumor site are currently evaluated.”
de Vicente, J. C., Rodríguez‐Santamarta, T., Rodrigo, J. P., Blanco‐Lorenzo, V., Allonca, E., & Garcia-Pedrero, J. M. (2018) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-18-0779 · Cited by 71
“OSCC is associated with poor prognosis and higher morbidity when diagnosed at advanced stages (11), and it has been considered to be a very immunosuppressive cancer.”
BackgroundHu, Z., Wen, Y., Ma, R., Chen, L., Zeng, X., Wen, W., & Sun, W. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.727762 · Cited by 65
Tenascin-C Orchestrates an Immune-Suppressive Tumor Microenvironment in Oral Squamous Cell Carcinoma
Spenlé, C., Loustau, T., Murdamoothoo, D., Erne, W., Divonne, S. B.-D. L. F., Veber, R., Petti, L., Bourdely, P., Mörgelin, M., Brauchle, E.-M., et al. (2020) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-20-0074 · Cited by 83
“The first-line treatment of HNSCC is surgery followed by radiotherapy and chemotherapy and recently immune checkpoint therapy where long-lasting effects are seen only in a fraction of patients (3, 4).”
BackgroundImmune-related gene signature for predicting the prognosis of head and neck squamous cell carcinoma
She, Y., Kong, X., Ge, Y.-P., Yin, P., Liu, Z.-Y., Chen, J.-Y., Gao, F., & Fang, S.-L. (2020) · Cancer Cell International · doi:10.1186/s12935-020-1104-7 · Cited by 63
Immune gene expression in head and neck squamous cell carcinoma patients.
Lecerf, C., Kamal, M., Vacher, S., Chemlali, W., Schnitzler, A., Morel, C., Dubot, C., Jeannot, E., Meseure, D., Klijanienko, J., et al. (2019) · European Journal of Cancer · doi:10.1016/j.ejca.2019.08.028 · Cited by 63
Al-Samadi, A., Poor, B., Tuomainen, K., Liu, V., Hyytiäinen, A., Sulymanova, I., Mesimaki, K., Wilkman, T., Mäkitie, A., Saavalainen, P., et al. (2019) · Experimental Cell Research · doi:10.1016/j.yexcr.2019.111508 · Cited by 63
Best Practice in Systemic Therapy for Head and Neck Squamous Cell Carcinoma
Oosting, S., & Haddad, R. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00815 · Cited by 63
“This led to approval of pembrolizumab for patients with a PD-L1 tumor proportion score (percentage of tumor cells with membranous PD-L1 staining) ≥50% in 2018 by the European Medicines Agency (EMA), while the FDA granted accelerated approval irrespective of PD-L1 expression back in 2016, based on the results of the ph…”
BackgroundBrand, F. Z. A., Suter, N., Adam, J., Faulques, B., Maietta, A., Soulières, D., & Blais, N. (2018) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-018-0332-z · Cited by 64
“In the treatment of recurrent or metastatic HNSCC, the incidence of grade 1 and 2 mucositis is between 1 and 2% with nivolumab and pembrolizumab with no grade 3 or 4 events reported so far [1, 2, 11].”
BackgroundCurrent studies of immunotherapy in head and neck cancer
Dogan, V., Rieckmann, T., Münscher, A., & Busch, C. (2018) · Clinical Otolaryngology · doi:10.1111/coa.12895 · Cited by 63
“Importantly, the duration of response was approximately 53 weeks.(15) The expansion cohort included 132 pre-treated patients with R/M HNSCC irrespective of PD-L1 expression or HPV status; 57% had ≥2 lines of prior systemic therapy for recurrent disease.”
BackgroundResultGalot, R., Tourneau, C. L., Guigay, J., Licitra, L. F., Tinhofer, I., Kong, A. H., Caballero, C. A., Fortpied, C., Bogaerts, J., Govaerts, A.-S., et al. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy452 · Cited by 67
“Pembrolizumab is also approved in the same indication by the Food and Drug Administration (FDA) [8].”
New developments in the management of head and neck cancer – impact of pembrolizumab
Saleh, K., Eid, R., Haddad, F., Khalifé-Saleh, N., & Kourie, H. (2018) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s125059 · Cited by 62
“This finding was not confirmed in the Phase II study KEYNOTE-055, where the response rates to pembrolizumab were similar in all PD-L1 expression subgroups.(44) Emerging data showed that clinical response to pembrolizumab in patients with HNSCC may be partly related to inhibition of PD-1/PD-L2 interactions.”
InfluentialImmunotherapy for Esophageal Squamous Cell Carcinoma
Kojima, T., & Doi, T. (2017) · Current Oncology Reports · doi:10.1007/s11912-017-0590-9 · Cited by 62
Tumor mutational burden as a predictive biomarker for checkpoint inhibitor immunotherapy
Lee, M., Samstein, R. M., Valero, C., Chan, T. A.-T., & Morris, L. G. T. (2019) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2019.1631136 · Cited by 76
Engels, E. A. (2019) · American Journal of Transplantation · doi:10.1111/ajt.15495 · Cited by 82
Cancer immunotherapy: the art of targeting the tumor immune microenvironment
da Silva, J. L., dos Santos, A. L. S., Nunes, N. C. C., da Silva, F. D. M. L., Ferreira, C. G., & de Melo, A. C. (2019) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-019-03894-3 · Cited by 62
Ma, H., Yang, W., Zhang, L., Liu, S., Zhao, M., Zhou, G., Wang, L., Jin, S., Zhang, Z., & Hu, J. (2018) · British Journal of Cancer · doi:10.1038/s41416-018-0352-y · Cited by 79
“Targeted therapies specific for programmed cell death 1 (PD1) and programmed cell death ligand 1 (PDL1) have shown surprising results for recurrent and/or metastatic HNSCC (R/M-HNSCC) in the CheckMate-141(4) and KEYNOTE-012 trials.(5) However, ICBs using nivolumab and pembrolizumab only resulted in a modest overall re…”
BackgroundImmune evasion mechanisms and immune checkpoint inhibition in advanced merkel cell carcinoma
Schadendorf, D., Nghiem, P., Bhatia, S., Hauschild, A., Saïag, P., Mahnke, L. A., Hariharan, S., & Kaufman, H. L. (2017) · OncoImmunology · doi:10.1080/2162402x.2017.1338237 · Cited by 66
“squamous cell carcinoma, another tumor with a viral etiology.(111) Anti–PD-1 and anti–PD-L1 antibodies have been inves-”
BackgroundChallenges and Opportunities in Adapting Clinical Trial Design for Immunotherapies
Siu, L. L., Ivy, S. P., Dixon, E. L., Gravell, A. E., Reeves, S. A., & Rosner, G. L. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-3079 · Cited by 75
Excellent response to chemotherapy post immunotherapy
Dwary, A. D., Master, S. R., Patel, A., Cole, C., Mansour, R. P., Mills, G. M., Koshy, N. V., Peddi, P., Burton, G. V., Hammoud, D. A., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.20030 · Cited by 66
“US Food and Drug Administration has approved immunotherapy mostly in the second line setting after progression on conventional chemotherapy for multiple stage IV cancers (Head and neck cancer [2,3], Non-small cell lung cancer [4], [5], Bladder cancer [6-10], Renal cell cancer [11] and melanoma [12,13]).”
BackgroundHepatocyte Growth Factor/c-Met Signaling in Head and Neck Cancer and Implications for Treatment
Rothenberger, N. J., & Stabile, L. P. (2017) · Cancers · doi:10.3390/cancers9040039 · Cited by 66
Lenouvel, D., González‐Moles, M. Á., Talbaoui, A., Ramos‐García, P., González‐Ruiz, L., Ruiz‐Ávila, I., & Montoya, J. A. G. (2019) · Oral Diseases · doi:10.1111/odi.13088 · Cited by 62
Seo, I., Lee, H. W., Byun, S. J., Park, J. Y., Min, H., Lee, S. H., Lee, J., Kim, S., & Bae, S. U. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-001610 · Cited by 65
“…strategy, several studies have recently evaluate various biomarkers, such as microsatellite instability (MSI), 12 13 mismatch repair (MMR) deficiency, 13 tumor mutational burden (TMB) 14 15 and immune biomarker scores, 16–18 for prediction of responses to immunotherapies, such as ICBs, in cancer.”
Miyauchi, S., Sanders, P. D., Guram, K., Kim, S. S., Paolini, F., Venuti, A., Cohen, E. E. W., Gutkind, J. S., Califano, J. A., & Sharabi, A. B. (2019) · Cancer Research · doi:10.1158/0008-5472.can-19-1771 · Cited by 73
Nivolumab for Patients With High-Risk Oral Leukoplakia
Hanna, G. J., Villa, A., Nandi, S. P., Shi, R., O’Neill, A., Liu, M., Quinn, C. T., Treister, N. S., Sroussi, H., Vacharotayangul, P., et al. (2023) · JAMA Oncology · doi:10.1001/jamaoncol.2023.4853 · Cited by 66
Sun, N.-Y., Chen, Y., Wu, W., Lin, H.-W., Chiang, Y., Chang, C.-F., Tai, Y., Hsu, H., Chen, C., Sun, W., et al. (2019) · Cancers · doi:10.3390/cancers11091400 · Cited by 65
Immune checkpoint inhibitors in the treatment of virus-associated cancers
Gao, P., Lazare, C., Cao, C., Meng, Y., Wu, P., Zhi, W., Lin, S., Wei, J.-C., Huang, X., Xi, L., et al. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0743-4 · Cited by 57
“A clinical trial (Keynote-012), which evaluated the safety and antitumor activity of pembrolizumab in patients with recurrent or metastatic (R/M) HNSCC, published results recently [15].”
Davar, D., Tarhini, A. A., & Kirkwood, J. M. (2017) · doi:10.1002/9781119468868.ch20 · Cited by 9
Metadata
- Authors
- Seiwert, T. Y., Burtness, B., Mehra, R., Weiss, J., Berger, R., Eder, J. P., Heath, K., McClanahan, T., Lunceford, J., Gause, C., Cheng, J. D., & Chow, L. Q.
- Affiliations
- University of Chicago (US)
- Fox Chase Cancer Center (US)
- University of North Carolina at Chapel Hill (US)
- Sheba Medical Center (IL)
- Yale Cancer Center (US)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- University of Washington (US)
- Corresponding author
- Seiwert, Tanguy Y
- ORCID
- Venue
- The Lancet Oncology
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 17
- Issue
- 7
- Pages
- 956-965
- ISSN
- 1470-2045 (ISSN-L)
- OpenAlex
- W2401455386
- Cited by
- 1,745
- References
- 0
- Citations by year
- 2026: 73 · 2025: 136 · 2024: 149 · 2023: 159 · 2022: 165 · 2021: 213 · 2020: 195 · 2019: 190 · 2018: 216 · 2017: 204 · 2016: 44
- FWCI
- 117.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet Oncology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Health Sciences › Medicine › Dermatology › Nonmelanoma Skin Cancer Studies
- Keywords
- pembrolizumab, PD-1 inhibitors, PD-L1 expression, immune checkpoint inhibitors, antitumour activity, drug safety and tolerability, immune-related adverse events, hyponatremia, elevated liver enzymes, overall response rate
- MeSH terms
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Carcinoma, Squamous Cell, Female, Follow-Up Studies, Head and Neck Neoplasms, Humans, Lymphatic Metastasis, Male, Middle Aged, Neoplasm Recurrence, Local, Neoplasm Staging, Prognosis, Safety, Survival Rate, Young Adult, Antibodies, Monoclonal, Humanized
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