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Review

An update: emerging drugs to treat squamous cell carcinomas of the head and neck

, &
Pages 283-299 | Received 16 Aug 2018, Accepted 29 Oct 2018, Published online: 16 Nov 2018

References

  • Stewart B, Wild CP World cancer report 2014. Health 2017.
  • Schlecht NF, Franco El, Pintos J, et al. Effect of smoking cessation and tobacco type on the risk of cancers of the upper aero-digestive tract in Brazil. Epidemiology. 1999;10:412–418.
  • Benson E, Li R, Eisele D, et al. The clinical impact of HPV tumor status upon head and neck squamous cell carcinomas. Oral Oncol. 2014;50:565–574.
  • Chaturvedi AK, D’Souza G, Gillison ML, et al. Burden of HPV-positive oropharynx cancers among ever and never smokers in the U.S. Population. Oral Oncol. 2016;60:61–67.
  • Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363:24–35.
  • Hong AM, Dobbins TA, Lee CS, et al. Human papillomavirus predicts outcome in oropharyngeal cancer in patients treated primarily with surgery or radiation therapy. Br J Cancer. 2010;103:1510–1517.
  • Rischin D, Young RJ, Fisher R, et al. Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. J Clin Oncol. 2010;28:4142–4148.
  • Gospodarowicz MK, Brierley JD, Wittekind C. TNM classification of malignant tumours, 8th ed. New Jersey: John Wiley & Sons; 2017.
  • Ndiaye C, Mena M, Alemany L, et al. HPV DNA, E6/E7 mRNA, and p16INK4a detection in head and neck cancers: a systematic review and meta-analysis. Lancet Oncol. 2014;15:1319–1331.
  • Chen AM, Felix C, Wang P-C, et al. Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx: a single-arm, phase 2 study. Lancet Oncol. 2017;18:803–811.
  • Colevas AD. Systemic therapy for metastatic or recurrent squamous cell carcinoma of the head and neck. J Natl Compr Canc Netw. 2015;13:e37–48.
  • Fung C, Grandis JR. Emerging drugs to treat squamous cell carcinomas of the head and neck. Expert Opin Emerg Drugs. 2010;15:355–373.
  • Consortium ICG. International network of cancer genome projects. Nature. 2010;464:993.
  • Agrawal N, Frederick MJ, Pickering CR, et al. Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science. 2011;333:1154-1157.
  • Stransky N, Egloff AM, Tward AD, et al. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011;333:1157–1160.
  • Network CGA. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015;517:576–582.
  • Johnson DE, O’Keefe RA, Grandis JR. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol. 2018;15:234–248.
  • Blasco MA, Svider PF, Raza SN, et al. Systemic therapy for head and neck squamous cell carcinoma: historical perspectives and recent breakthroughs. Laryngoscope. 2017;127:2565–2569.
  • Zumsteg ZS, Luu M, Yoshida EJ, et al. Combined high-intensity local treatment and systemic therapy in metastatic head and neck squamous cell carcinoma: an analysis of the National Cancer Data Base. Cancer. 2017;123:4583–4593.
  • Szabó B, Nelhűbel GA, Kárpáti A, et al. Clinical significance of genetic alterations and expression of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinomas. Oral Oncol. 2011;47:487–496.
  • Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354:567–578.
  • Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252.
  • Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. J Clin Oncol. 2015;33:1974–1982.
  • Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non–small-cell lung cancer. N Engl J Med. 2015;373:123–135.
  • Herbst RS, Baas P, Kim D-W, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387:1540–1550.
  • Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372:320–330.
  • Forastiere AA, Goepfert H, Maor M, et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003;349:2091–2098.
  • Popovtzer A, Burnstein H, Stemmer S, et al. Phase II organ-preservation trial: concurrent cisplatin and radiotherapy for advanced laryngeal cancer after response to docetaxel, cisplatin, and 5-fluorouracil-based induction chemotherapy. Head Neck. 2017;39:227–233.
  • Posner MR, Hershock DM, Blajman CR et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007;357:1705–1715.
  • Vermorken JB, Remenar E, Van Herpen C, et al. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med. 2007;357:1695–1704.
  • Haddad R, O’Neill A, Rabinowits G, et al. Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial. Lancet Oncol. 2013;14:257–264.
  • Zhang L, Jiang N, Shi Y, et al. Induction chemotherapy with concurrent chemoradiotherapy versus concurrent chemoradiotherapy for locally advanced squamous cell carcinoma of head and neck: a meta-analysis. Sci Rep. 2015;5:10798.
  • Bernier J, Cooper JS, Pajak TF, et al. Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck. 2005;27:843–850.
  • Network NCC. NCCN guidelines: head and neck cancer, version 1. Fort Washington, PA: National Comprehensive Cancer Network;2018.
  • Huang J, Zhang J, Shi C, et al. Survival, recurrence and toxicity of HNSCC in comparison of a radiotherapy combination with cisplatin versus cetuximab: a meta-analysis. BMC Cancer. 2016;16:689.
  • Marur S, Forastiere AA. Head and neck cancer: changing epidemiology, diagnosis, and treatment. Mayo Clin Proc. 2008;83:489–501.
  • Saloura V, Cohen EE, Licitra L, et al. An open-label single-arm, phase II trial of zalutumumab, a human monoclonal anti-EGFR antibody, in patients with platinum-refractory squamous cell carcinoma of the head and neck. Cancer Chemother Pharmacol. 2014;73:1227–1239.
  • Bossi P, Alfieri S. Investigational drugs for head and neck cancer. Expert Opin Investig Drugs. 2016;25:797–810.
  • Leemans CR, Braakhuis BJ, Brakenhoff RH. The molecular biology of head and neck cancer. Nat Rev Cancer. 2011;11:9.
  • Chung CH, Parker JS, Ely K, et al. Gene expression profiles identify epithelial-to-mesenchymal transition and activation of nuclear factor-κB signaling as characteristics of a high-risk head and neck squamous cell carcinoma. Cancer Res. 2006;66:8210–8218.
  • Schneider-Merck T, van Bueren JJL, Berger S, et al. Human IgG2 antibodies against epidermal growth factor receptor effectively trigger antibody-dependent cellular cytotoxicity but, in contrast to IgG1, only by cells of myeloid lineage. J Immunol. 2010;184:512–520.
  • Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010;11:21–28.
  • Burtness B, Goldwasser MA, Flood W, et al. Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol. 2005;23:8646–8654.
  • Vermorken JB, Trigo J, Hitt R, et al. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J Clin Oncol. 2007;25:2171–2177.
  • Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359:1116–1127.
  • Vermorken JB, Stöhlmacher-Williams J, Davidenko I, et al. Cisplatin and fluorouracil with or without panitumumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SPECTRUM): an open-label phase 3 randomised trial. Lancet Oncol. 2013;14:697–710.
  • Wirth LJ, Dakhil SR, Kornek G, et al. PARTNER: a randomized phase II study of docetaxel/cisplatin (doc/cis) chemotherapy with or without panitumumab (pmab) as first-line treatment (tx) for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). J Clin Oncol 2013;31:suppl. 6029.
  • Sacco AG, Worden FP. Molecularly targeted therapy for the treatment of head and neck cancer: a review of the ErbB family inhibitors. OncoTargets Ther. 2016;9:1927.
  • Cohen EE, Licitra LF, Fayette J, et al. Biomarker analysis in recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients (pts) treated with second-line afatinib versus methotrexate (MTX): LUX-Head & Neck 1 (LUX-H&N1). J Clin Oncol 2015;33:suppl. 6023.
  • Seiwert TY, Fayette J, Cupissol D, et al. A randomized, phase II study of afatinib versus cetuximab in metastatic or recurrent squamous cell carcinoma of the head and neck. Ann Oncol. 2014;25:1813–1820.
  • Chung CH, Rudek MA, Kang H, et al. A phase I study afatinib/carboplatin/paclitaxel induction chemotherapy followed by standard chemoradiation in HPV-negative or high-risk HPV-positive locally advanced stage III/IVa/IVb head and neck squamous cell carcinoma. Oral Oncol. 2016;53:54–59.
  • Abdul Razak AR, Soulieres D, Laurie SA, et al. A phase II trial of dacomitinib, an oral pan-human EGF receptor (HER) inhibitor, as first-line treatment in recurrent and/or metastatic squamous-cell carcinoma of the head and neck. Ann Oncol. 2013;24:761–769.
  • Kim HS, Kwon HJ, Jung I, et al. Phase II clinical and exploratory biomarker study of dacomitinib in patients with recurrent and/or metastatic squamous cell carcinoma of head and neck. Clin Cancer Res. 2015;21:544–552.
  • Bauman JE, Arias-Pulido H, Lee S-J, et al. Phase II study of temsirolimus and erlotinib in patients (pts) with recurrent/metastatic (R/M), platinum-refractory head and neck squamous cell carcinoma (HNSCC). J Clin Oncol. 2012;30:suppl. 5549.
  • Cohen EE, Davis DW, Karrison TG, et al. Erlotinib and bevacizumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck: a phase I/II study. Lancet Oncol. 2009;10:247–257.
  • Van Allen EM, Lui VW, Egloff AM, et al. Genomic correlate of exceptional erlotinib response in head and neck squamous cell carcinoma. JAMA Oncol. 2015;1:238–244.
  • Stewart J, Cohen E, Licitra L, et al. Phase III study of gefitinib compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck. J Clin Oncol. 2009;27:1864–1871.
  • de Souza JA, Davis DW, Zhang Y, et al. A phase II study of lapatinib in recurrent/metastatic squamous cell carcinoma of the head and neck. Clin Cancer Res. 2012;18:2336–2343.
  • Limaye S, Riley S, Zhao S, et al. A randomized phase II study of docetaxel with or without vandetanib in recurrent or metastatic squamous cell carcinoma of head and neck (SCCHN). Oral Oncol. 2013;49:835–841.
  • Duray A, Demoulin S, Hubert P, et al. Immune suppression in head and neck cancers: a review. Clin Dev Immunol. 2011;2010:701657.
  • Fessas P, Lee H, Ikemizu S, et al. A molecular and preclinical comparison of the PD-1–targeted T-cell checkpoint inhibitors nivolumab and pembrolizumab. Semin Oncol. 2017. p. 136–140.
  • Cohen E, Harrington K, Le Tourneau C, et al. LBA45_PRPembrolizumab (pembro) vs standard of care (SOC) for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC): phase 3 KEYNOTE-040 trial. Ann Oncol. 2017;28:suppl.5.
  • Ferris RL, Blumenschein G Jr., Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375:1856–1867.
  • Bauml J, Seiwert TY, Dg P, et al. Pembrolizumab for platinum- and cetuximab-refractory head and neck cancer: results from a single-arm, phase II study. J Clin Oncol. 2017;35:1542–1549.
  • Seiwert TY, Burtness B, Mehra R, et al. 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. Lancet Oncol. 2016;17:956–965.
  • Chow LQ, Haddad R, Gupta S, et al. Antitumor activity of pembrolizumab in biomarker-unselected patients with recurrent and/or metastatic head and neck squamous cell carcinoma: results from the phase Ib KEYNOTE-012 expansion cohort. J Clin Oncol. 2016;34:3838–3845.
  • Klochikhin A, Greil R, Cohen E, et al. 11TiP Phase 3 trial of pembrolizumab as a first-line treatment in subjects with recurrent/metastatic head and neck squamous cell carcinoma: KEYNOTE-048. Ann Oncol. 2015;26:viii5–viii.
  • Gillison ML, Blumenschein G, Fayette J et al. Nivolumab (nivo) vs investigator’s choice (IC) for recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): CheckMate-141. AACR Annual Meeting; New Orleans, LA, 2016;CT099a.
  • Harrington KJ, Ferris RL, Blumenschein JG, et al. Nivolumab versus standard, single-agent therapy of investigator’s choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality-of-life results from a randomised, phase 3 trial. Lancet Oncol. 2017;18:1104–1115.
  • Boeckx C, Baay M, Wouters A, et al. Anti-epidermal growth factor receptor therapy in head and neck squamous cell carcinoma: focus on potential molecular mechanisms of drug resistance. Oncologist. 2013;18:850–864.
  • Ferris RL, Blumenschein G, Harrington K, et al. Abstract CT021: tumor-associated immune cell PD-L1 expression and peripheral immune profiling: analyses from CheckMate. Cancer Res 2017;77:suppl.13.
  • Topalian SL, Taube JM, Anders RA, et al. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat Rev Cancer. 2016;16:275.
  • De Felice F, Urbano TG. New drug development in head and neck squamous cell carcinoma: the PI3-K inhibitors. Oral Oncol. 2017;67:119–123.
  • Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell. 2012;149:274–293.
  • Squarize CH, Castilho RM, Abrahao AC, et al. PTEN deficiency contributes to the development and progression of head and neck cancer. Neoplasia. 2013;15:461–471.
  • Lui VW, Hedberg ML, Li H, et al. Frequent mutation of the PI3K pathway in head and neck cancer defines predictive biomarkers. Cancer Discov. 2013;3:761–769.
  • Seiwert TY, Zuo Z, Keck MK, et al. Integrative and comparative genomic analysis of HPV-positive and HPV-negative head and neck squamous cell carcinomas. Clin Cancer Res. 2015;21:632–641.
  • Wheeler DL, Huang S, Kruser TJ, et al. Mechanisms of acquired resistance to cetuximab: role of HER (ErbB) family members. Oncogene. 2008;27:3944.
  • Chung CH, Guthrie V, Masica D, et al. Genomic alterations in head and neck squamous cell carcinoma determined by cancer gene-targeted sequencing. Ann Oncol. 2015;26:1216–1223.
  • Soulieres D, Faivre SJ, Mesia R, et al. BERIL-1: A phase II, placebo-controlled study of buparlisib (BKM120) plus paclitaxel in patients with platinum-pretreated recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Am Soc Clin Oncol. 2016.
  • Jimeno A, Shirai K, Choi M, et al. A randomized, phase II trial of cetuximab with or without PX-866, an irreversible oral phosphatidylinositol 3-kinase inhibitor, in patients with relapsed or metastatic head and neck squamous cell cancer. Ann Oncol. 2014;26:556–561.
  • Jimeno A, Bauman JE, Weissman C, et al. A randomized, phase 2 trial of docetaxel with or without PX-866, an irreversible oral phosphatidylinositol 3-kinase inhibitor, in patients with relapsed or metastatic head and neck squamous cell cancer. Oral Oncol. 2015;51:383–388.
  • Markham A. Copanlisib: first global approval. Drugs. 2017;77:2057–2062.
  • Zheng Y, Jiang Y. mTOR inhibitors at a glance. Mol Cell Pharmacol. 2015;7:15.
  • Hudes G, Garducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007;356:2271–2281.
  • Kollmannsberger C, Hirte H, Siu L, et al. Temsirolimus in combination with carboplatin and paclitaxel in patients with advanced solid tumors: a NCIC-CTG, phase I, open-label dose-escalation study (IND 179). Ann Oncol. 2011;23:238–244.
  • Ramalingam SS, Harvey RD, Saba N, et al. Phase 1 and pharmacokinetic study of everolimus, a mammalian target of rapamycin inhibitor, in combination with docetaxel for recurrent/refractory nonsmall cell lung cancer. Cancer. 2010;116:3903–3909.
  • Chung CH, Wang H, Tsottles N, et al. A phase I study of everolimus in combination with cetuximab and cisplatin as first-line therapy in recurrent and metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). J Clin Oncol. 2012;30:suppl.e16061 .
  • Shirai K, Day TA, Szabo E, et al. A pilot, single arm, prospective trial using neoadjuvant rapamycin prior to definitive therapy in head and neck squamous cell carcinoma.J Clin Oncol. 2015:33:suppl.6071
  • Grünwald V, Keilholz U, Boehm A, et al. TEMHEAD: a single-arm multicentre phase II study of temsirolimus in platin- and cetuximab refractory recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) of the German SCCHN Group (AIO). Annal Oncol. 2014;26:561–567.
  • Fury MG, Xiao H, Baxi SS, et al. A phase II trial of temsirolimus plus low-dose weekly carboplatin and paclitaxel for recurrent/metastatic HNSCC. J Clin Oncol. 2014;32:suppl.6019 .
  • Bauman JE, Arias-Pulido H, Lee S-J, et al. A phase II study of temsirolimus and erlotinib in patients with recurrent and/or metastatic, platinum-refractory head and neck squamous cell carcinoma. Oral Oncol. 2013;49:461–467.
  • Massarelli E, Lin H, Ginsberg L, et al. Phase II trial of everolimus and erlotinib in patients with platinum-resistant recurrent and/or metastatic head and neck squamous cell carcinoma. Ann Oncol. 2015;26:1476–1480.
  • Cohen E, Hong D, WiseDraper T, et al. 1135OPhase 1b/2 Study (SCORES) assessing safety, tolerability, and preliminary anti-tumor activity of durvalumab plus AZD9150 or AZD5069 in patients with advanced solid malignancies and squamous cell carcinoma of the head and neck (SCCHN). Ann Oncol.2017;28:suppl.5.
  • Kyzas PA, Cunha IW, Ioannidis JP. Prognostic significance of vascular endothelial growth factor immunohistochemical expression in head and neck squamous cell carcinoma: a meta-analysis. Clin Cancer Res. 2005;11:1434–1440.
  • McGee MC, Hamner JB, Williams RF, et al. Improved intratumoral oxygenation through vascular normalization increases glioma sensitivity to ionizing radiation. Int J Radiat Oncol Biol Phys. 2010;76:1537–1545.
  • Argiris A, Kotsakis A, Hoang T, et al. Cetuximab and bevacizumab: preclinical data and phase II trial in recurrent or metastatic squamous cell carcinoma of the head and neck. Ann Oncol. 2012;24:220–225.
  • Fury MG, Lee NY, Sherman E, et al. A phase 2 study of bevacizumab with cisplatin plus intensity‐modulated radiation therapy for stage III/IVB head and neck squamous cell cancer. Cancer. 2012;118:5008–5014.
  • Argiris A, Ghebremichael M, Gilbert J, et al. Phase III randomized, placebo-controlled trial of docetaxel with or without gefitinib in recurrent or metastatic head and neck cancer: an eastern cooperative oncology group trial. J Clin Oncol. 2013;31:1405.
  • Shapiro GI. Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol. 2006;24:1770–1783.
  • Hamilton E, Infante JR. Targeting CDK4/6 in patients with cancer. Cancer Treat Rev. 2016;45:129–138.
  • Asghar U, Witkiewicz AK, Turner NC, et al. The history and future of targeting cyclin-dependent kinases in cancer therapy. Nat Rev Drug Discov. 2015;14:130.
  • Flaherty KT, LoRusso PM, DeMichele AM, et al. Phase 1, dose-escalation trial of the oral cyclin-dependent kinase 4/6 inhibitor PD 0332991, administered using a 21-day schedule in patients with advanced cancer. Clin Cancer Res. 2011;18:568–576.
  • Patnaik A, Rosen LS, Tolaney SM, et al. Efficacy and safety of abemaciclib, an inhibitor of CDK4 and CDK6, for patients with breast cancer, non–small cell lung cancer, and other solid tumors. Cancer Discov. 2016.
  • Infante JR, Shapiro G, Witteveen P, et al. A phase I study of the single-agent CDK4/6 inhibitor LEE011 in pts with advanced solid tumors and lymphomas. J Clin Oncol. 2014;32:suppl.2528 .
  • Shapiro G, Rosen LS, Tolcher AW, et al. A first-in-human phase I study of the CDK4/6 inhibitor, LY2835219, for patients with advanced cancer. J Clin Oncol. 2013;31:suppl.2500 .
  • Choschzick M, Hess S, Tennstedt P, et al. Role of cyclin D1 amplification and expression in vulvar carcinomas. Hum Pathol. 2012;43:1386–1393.
  • Michel L, Ley J, Wildes TM, et al. Phase I trial of palbociclib, a selective cyclin dependent kinase 4/6 inhibitor, in combination with cetuximab in patients with recurrent/metastatic head and neck squamous cell carcinoma. Oral Oncol. 2016;58:41–48.
  • Adkins D, Oppelt PJ, Ley JC, et al. Multicenter phase II trial of palbociclib, a selective cyclin dependent kinase (CDK) 4/6 inhibitor, and cetuximab in platinum-resistant HPV unrelated (−) recurrent/metastatic head and neck squamous cell carcinoma (RM HNSCC). Am Soc Clin Oncol. 2018.
  • Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Annu Rev Immunol. 2005;23:515–548.
  • Latchman Y, Wood CR, Chernova T, et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol. 2001;2:261.
  • Cavalieri S, Rivoltini L, Bergamini C, et al. Immuno-oncology in head and neck squamous cell cancers: news from clinical trials, emerging predictive factors and unmet needs. Cancer Treat Rev. 2018;65:78–86.
  • Chen DS, Irving BA, Hodi FS. Molecular pathways: next generation immunotherapy: inhibiting programmed death-ligand 1 and programmed death-1. Clin Cancer Res. 2012;18:6580–6587.
  • Bahleda R, Braiteh F, Balmanoukian A, et al. 1044O Long-term safety and clinical outcomes of atezolizumab in head and neck cancer: phase Ia trial results. Ann Oncol. 2017;28:suppl.5.
  • Zandberg D, Algazi A, Jimeno A, et al. 1042ODurvalumab for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): preliminary results from a single-arm, phase 2 study. Ann Oncol. 2017;28:suppl. 5.
  • Alfieri S, Cavalieri S, Licitra L. Immunotherapy for recurrent/metastatic head and neck cancer. Curr Opin Otolaryngol Head Neck Surg. 2018;26:152–156.
  • Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373:23–34.
  • Swanson MS, Sinha UK. Rationale for combined blockade of PD-1 and CTLA-4 in advanced head and neck squamous cell cancer–review of current data. Oral Oncol. 2015;51:12–15.
  • Aspeslagh S, Postel-Vinay S, Rusakiewicz S, et al. Rationale for anti-OX40 cancer immunotherapy. Eur J Cancer. 2016;52:50–66.
  • Dogan V, Rieckmann T, Munscher A, et al. Current studies of immunotherapy in head and neck cancer. Clin Otolaryngol. 2018;43:13–21.
  • Curti BD, Kovacsovics-Bankowski M, Morris N, et al. OX40 is a potent immune-stimulating target in late-stage cancer patients. Cancer Res. 2013;73:7189–7198.
  • Schaer DA, Budhu S, Liu C, et al. GITR pathway activation abrogates tumor immune suppression through loss of regulatory T-cell lineage stability. Cancer Immunol Res. 2013;1:320–331.
  • Fisher TS, Kamperschroer C, Oliphant T, et al. Targeting of 4-1BB by monoclonal antibody PF-05082566 enhances T-cell function and promotes anti-tumor activity. Cancer Immunol Immunother. 2012;61:1721–1733.
  • Vonderheide RH, Glennie MJ. Agonistic CD40 antibodies and cancer therapy. Clin Cancer Res. 2013;19:1035–1043.
  • Mahoney KM, Rennert PD, Freeman GJ. Combination cancer immunotherapy and new immunomodulatory targets. Nat Rev Drug Discov. 2015;14:561.
  • Hamid O, Bauer TM, Spira AI, et al. Epacadostat plus pembrolizumab in patients with SCCHN: preliminary phase I/II results from ECHO-202/KEYNOTE-037. Am Soc Clin Oncol. 2017.
  • Chow LQ, Morishima C, Eaton KD, et al. Phase Ib trial of the toll-like receptor 8 agonist, motolimod (VTX-2337), combined with cetuximab in patients with recurrent or metastatic SCCHN. Clin Cancer Res. 2017;23:2442–2450.
  • Glisson B, Massarelli E, William W, et al. 1136O Nivolumab and ISA 101 HPV vaccine in incurable HPV-16+ cancer. Ann Oncol. 2017;28:suppl.5.
  • Rabinowits G, Haddad RI. Overcoming resistance to EGFR inhibitor in head and neck cancer: a review of the literature. Oral Oncol. 2012;48:1085–1089.
  • Yonesaka K, Zejnullahu K, Okamoto I, et al. Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab. Sci Transl Med. 2011;3:99ra86–99ra86.
  • Haddad Y, Choi W, McConkey DJ. Delta-crystallin enhancer binding factor 1 controls the epithelial to mesenchymal transition phenotype and resistance to the epidermal growth factor receptor inhibitor erlotinib in human head and neck squamous cell carcinoma lines. Clin Cancer Res. 2009;15:532–542.
  • Timpson P, Wilson AS, Lehrbach GM, et al. Aberrant expression of cortactin in head and neck squamous cell carcinoma cells is associated with enhanced cell proliferation and resistance to the epidermal growth factor receptor inhibitor gefitinib. Cancer Res. 2007;67:9304–9314.
  • Fernandez-Mateos J, Seijas-Tamayo R, Mesia R, et al. Epidermal growth factor receptor (EGFR) pathway polymorphisms as predictive markers of cetuximab toxicity in locally advanced head and neck squamous cell carcinoma (HNSCC) in a Spanish population. Oral Oncol. 2016;63:38–43.
  • Zhang X, Fan J, Li Y, et al. Polymorphisms in epidermal growth factor receptor (EGFR) and AKT1 as possible predictors of clinical outcome in advanced non-small-cell lung cancer patients treated with EGFR tyrosine kinase inhibitors. Tumour Biol. 2016;37:1061–1069.
  • Rebucci M, Peixoto P, Dewitte A, et al. Mechanisms underlying resistance to cetuximab in the HNSCC cell line: role of AKT inhibition in bypassing this resistance. Int J Oncol. 2011;38:189–200.
  • Licitra L, Storkel S, Kerr KM, et al. Predictive value of epidermal growth factor receptor expression for first-line chemotherapy plus cetuximab in patients with head and neck and colorectal cancer: analysis of data from the EXTREME and CRYSTAL studies. Eur J Cancer. 2013;49:1161–1168.
  • Jhaveri K, Juric D, Saura C, et al. Abstract CT046: a phase I basket study of the PI3K inhibitor taselisib (GDC-0032) in PIK3CA-mutated locally advanced or metastatic solid tumors.  Cancer Res.2018;78:suppl.13.
  • Zou W. Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer. 2005;5:263.
  • Keck MK, Zuo Z, Khattri A, et al. Integrative analysis of head and neck cancer identifies two biologically distinct HPV and three non-HPV subtypes. Clin Cancer Res. 2015;21:870–881.
  • Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009;9:162.
  • Davis RJ, Van Waes C, Allen CT. Overcoming barriers to effective immunotherapy: MDSCs, TAMs, and Tregs as mediators of the immunosuppressive microenvironment in head and neck cancer. Oral Oncol. 2016;58:59–70.
  • Rodriguez PC, Hernandez CP, Quiceno D, et al. Arginase I in myeloid suppressor cells is induced by COX-2 in lung carcinoma. J Exp Med. 2005;202:931–939.
  • Garrity T, Pandit R, Wright MA, et al. Increased presence of CD34+ cells in the peripheral blood of head and neck cancer patients and their differentiation into dendritic cells. Int J Cancer. 1997;73:663–669.
  • Lee YS, Park JY, Cho KJ, et al. Composition of inflammatory cells regulating the response to concurrent chemoradiation therapy for HPV (+) tonsil cancer. Oral Oncol. 2015;51:1113–1119.
  • Chanmee T, Ontong P, Konno K, et al. Tumor-associated macrophages as major players in the tumor microenvironment. Cancers. 2014;6:1670–1690.
  • Mok S, Koya RC, Tsui C, et al. Inhibition of CSF-1 receptor improves the antitumor efficacy of adoptive cell transfer immunotherapy. Cancer Res. 2014;74:153–161.
  • Liu C, Workman CJ, Vignali DA. Targeting regulatory T cells in tumors. FEBS J. 2016;283:2731–2748.
  • Tanaka A, Sakaguchi S. Regulatory T cells in cancer immunotherapy. Cell Res. 2017;27:109.
  • Selby MJ, Engelhardt JJ, Quigley M, et al. Anti-CTLA-4 antibodies of IgG2a isotype enhance antitumor activity through reduction of intratumoral regulatory T cells. Cancer Immunol Res. 2013;1:32–42.
  • Sugiyama D, Nishikawa H, Maeda Y, et al. Anti-CCR4 mAb selectively depletes effector-type FoxP3+ CD4+ regulatory T cells, evoking antitumor immune responses in humans. Proc Natl Acad Sci USA. 2013;110:17945–17950.
  • Park B, Yee C, Lee K-M. The effect of radiation on the immune response to cancers. Int J Mol Sci. 2014;15:927–943.
  • Uppaluri R, Zolkind P, Lin T, et al. Neoadjuvant pembrolizumab in surgically resectable, locally advanced HPV negative head and neck squamous cell carcinoma (HNSCC). J Clin Oncol. 2017;35: suppl.6012.
  • Ferris R, Gonçalves A, Baxi S, et al. LBA46An open-label, multicohort, phase 1/2 study in patients with virus-associated cancers (CheckMate 358): safety and efficacy of neoadjuvant nivolumab in squamous cell carcinoma of the head and neck (SCCHN). Ann Oncol. 2017;28:suppl.5.

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