Head and Neck TumorsHead and Neck TumorsОпухоли головы и шеи2222-14682411-4634Publishing House ABV Press55910.17650/2222-1468-2020-10-3-41-47DIAGNOSIS AND TREATMENT OF HEAD AND NECK TUMORSДИАГНОСТИКА И ЛЕЧЕНИЕ ОПУХОЛЕЙ ГОЛОВЫ И ШЕИCurrent trends in the immunotherapy of metastatic and recurrent squamous cell carcinoma of the head and neckСовременные тенденции в иммунотерапии метастатического и рецидивного плоскоклеточного рака головы и шеиKostalanovaYu. V.КосталановаЮ В.
Russian Federation

50 Solnechnaya St., Samara 443031

Юлия Владимировна Косталанова

443031 Самара, ул. Солнечная, 50

kostalanova@yandex.ruhttps://orcid.org/0000-0003-4944-2507GaninaK. A.ГанинаК. А.
Russian Federation

89 Chapaevskaya St., Samara 443099

443099 Самара, ул. Чапаевская, 89

https://orcid.org/0000-0002-2182-5429MakhoninA. A.МахонинА. А.
Russian Federation

50 Solnechnaya St., Samara 443031, 

89 Chapaevskaya St., Samara 443099

443031 Самара, ул. Солнечная, 50, 

443099 Самара, ул. Чапаевская, 89

https://orcid.org/0000-0002-5321-6070GabrielyanA. G.ГабриелянА. Г.
Russian Federation

50 Solnechnaya St., Samara 443031, 

89 Chapaevskaya St., Samara 443099

443031 Самара, ул. Солнечная, 50, 

443099 Самара, ул. Чапаевская, 89

Samara Regional Clinical Oncology DispensaryГБУЗ «Самарский областной клинический онкологический диспансер»Samara State Medical University, Ministry of Health of RussiaФГБОУ ВО «Самарский государственный медицинский университет» Минздрава России1611202010341471611202016112020Copyright ©; 2020, Kostalanova Y.V., Ganina K.A., Makhonin A.A., Gabrielyan A.G.Copyright ©; 2020, Косталанова Ю.В., Ганина К.А., Махонин А.А., Габриелян А.Г.2020Kostalanova Y.V., Ganina K.A., Makhonin A.A., Gabrielyan A.G.Косталанова Ю.В., Ганина К.А., Махонин А.А., Габриелян А.Г.https://creativecommons.org/licenses/by/4.0https://ogsh.abvpress.ru/jour/article/view/559

The immune system plays a key role in the development and progression of head and neck squamous cell carcinoma. Understanding the dysregulation and blockage of the immune system of malignant tumors in this location can improve treatment outcomes. A special group is made up of patients who have a widespread process and relapse after chemotherapy with platinum drugs, because they have a very poor prognosis and limitations in the possibilities of further treatment. To date, the most important data relate to drugs acting on the PD-1 (programmed cell death protein 1)/PD-L1 (programmed death ligand 1) immune checkpoints, which are used by the tumor to block the immune system, which have allowed to increase the effectiveness of treatment. The article presents a clinical case demonstrating the effectiveness of the use of checkpoint inhibitors after the use of platinum preparations.

Иммунная система играет ключевую роль в возникновении и прогрессировании плоскоклеточного рака головы и шеи. Понимание механизмов нарушения функционирования иммунной системы при развитии злокачественных опухолей данной локализации может улучшить результаты лечения. Особую группу составляют пациенты с распространенным процессом и рецидивами после терапии препаратами платины, потому что для них характерен очень плохой прогноз и возможности их дальнейшего лечения крайне ограничены. На сегодняшний день наиболее перспективны препараты, действующие на контрольные точки иммунитета PD-1 (белок программируемой клеточной смерти 1) и PD-L1 (лиганд белка программируемой клеточной смерти 1), которые используются опухолью для блокирования иммунной системы. Эти препараты позволили увеличить эффективность лечения пациентов. В статье описан клинический случай, демонстрирующий эффективность применения ингибиторов иммунных контрольных точек после применения препаратов платины.

immunotherapypembrolizumabnivolumabprogrammed cell death protein 1PD-1programmed cell death ligand 1PD-L1biomarkersиммунотерапияпембролизумабниволумаббелок программируемой клеточной смерти PD-1лиганд белка запрограммированной клеточной смерти PD-L1биомаркерыBray F., Ferlay J., Soerjomataram I. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68(6):394–424. DOI: 10.3322/caac.21492.Leemans C.R., Braakhuis B.J., Brakenhoff R.H. The molecular biology of head and neck cancer. Nat Rev Cancer 2011;11:9–22. DOI: 10.1038/nrc2982.Hashibe M., Brennan P., Chuang S.C. et al. Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Cancer Epidemiol Biomarkers Prev 2009;18(2):541–50. DOI: 10.1158/1055-9965.EPI-08-0347.Pan C., Issaeva N., Yarbrough W.G. HPV-driven oropharyngeal cancer: current knowledge of molecular biology and mechanisms of carcinogenesis. Cancers Head Neck 2018;3:12. DOI: 10.1186/s41199-018-0039-3.Gameiro S.F., Ghasemi F., Barrett J.W. et al. Treatment-naive HPV+ head and neck cancers display a T-cell-inflamed phenotype distinct from their HPV-counterparts that has implications for immunotherapy. Oncoimmunology 2018;7:e1498439. DOI: 10.1080/2162402x.2018.1498439.Kian Ang K., Harris J., Wheeler R. et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 2010;363(1):24–35. DOI: 10.1056/NEJMoa0912217.Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2017. CA Cancer J Clin 2017; 67(1):7–30. DOI: 10.3322/caac.21387.State of cancer care in Russia in 2018. Ed. by A.D. Kaprin, V.V. Starinsky, G.V. Petrova. Moscow, 2019. 236 c. (In Russ.).Состояние онкологической помощи населению России в 2018 году. Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М., 2019. 236 c.Denaro N., Russi E.G., Adamo V., Merlano M.C. State-of-the-art and emerging treatment options in the management of head and neck cancer: news from 2013. Oncology 2014;86:212–29. DOI: 10.1159/000357712.Haddad R.I., Shin D.M. Recent advances in head and neck cancer. N Engl J Med 2008;359:1143–54. DOI: 10.1056/NEJMra0707975.Guigay J., Fayette J., Dillies A.F. et al. Cetuximab, docetaxel, and cisplatin as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma: a multicenter, phase II GORTEC study. Ann Oncol 2015;26(9):1941–7. DOI: 10.1093/annonc/mdv268.De Stefani A., Forni G., Ragona R. Improved survival with perilymphatic interleukin 2 in patients with resectable squamous cell carcinoma of the oral cavity and oropharynx. Cancer 2002;95(1):90–7. DOI: 10.1002/cncr.10654.Whiteside T.L., Letessier E., Hirabayashi H. et al. Evidence for local and systemic activation of immune cells by peritumoral injections of interleukin 2 in patients with advanced squamous cell carcinoma of the head and neck. Cancer Res 1993;53(23):5654–62.Dadian G., Riches P., Henderson D. et al. Immune changes in peripheral blood resulting from locally directed interleukin-2 therapy in squamous cell carcinoma of the head and neck. Eur J Cancer Part B Oral Oncol 1993;29B(1):29–34. DOI: 10.1016/0964-1955(93)90007-2.Fridman W.H., Zitvogel L., SautèsFridman C., Kroemer G. The immune contexture in cancer prognosis and treatment. Nat Rev Clin Oncol 2017;14(12): 717–34. DOI: 10.1038/nrclinonc.2017.101.Burnet F.M. Immunological Recognition of Self: Such recognition suggests a relationship with processes through which functional integrity is maintained. Science 1961;133(3449):307–11. DOI: 10.1126/science.133.3449.307.Burtness B., Harrington K.J., Greil R. et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet 2019;394(10212):1915–28. DOI: 10.1016/S0140-6736(19)32591-7.Economopoulou P., Agelaki S., Perisanidis C. et al. The promise of immunotherapy in head and neck squamous cell carcinoma. Ann Oncol 2016;27:1675–85. DOI: 10.1093/annonc/mdw226.Schumacher T.N., Schreiber R.D. Neoantigens in cancer immunotherapy. Science 2015;348(6230):69–74. DOI: 10.1126/science.aaa4971.Mandal R., Şenbabaoğlu Y., Desrichard A. et al. The head and neck cancer immune landscape and its immunotherapeutic implications. JCI Insight 2016;1(17). DOI: 10.1172/jci.insight.89829.Tumeh P.C., Harview C.L., Yearley J.H. et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 2014;515:568–71. DOI: 10.1038/nature13954.Herbst R.S., Soria J.C., Kowanetz M. et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 2014;515:563–7. DOI: 10.1038/nature14011.Samstein R.M., Lee C.-H., Shoushtari A.N. et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet 2019;51(2):202–6. DOI: 10.1038/s41588-018-0312-8.Lawrence M.S., Stojanov P., Polak P. et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 2013;499:214–8. DOI: 10.1038/nature12213.Alexandroff A.B., Nicholson S., Patel P.M., Jackson A.M. Recent advances in bacillus Calmette–Guerin immunotherapy in bladder cancer. Immunotherapy 2010;2:551–60. DOI: 10.2217/imt.10.32.Cohen E.E.W., Bell R.B., Bifulco C.B. et al. The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC). J Immunother Cancer 2019; 7:184. DOI: 10.1186/s40425-019-0662-5.Seiwert T.Y., 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;17:956–65. DOI: 10.1016/s1470-2045(16)30066-3.Mehra R., Seiwert T.Y., Gupta S. et al. Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012. Br J Cancer 2018;119:153–9. DOI: 10.1038/s41416-018-0131-9.Leon X., Hitt R., Constenla M. et al. A retrospective analysis of the outcome of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck refractory to a platinum-based chemotherapy. Clin Oncol (R Coll Radiol) 2005;17:418–24. DOI: 10.1016/j.clon.2005.02.014.Lala M., Chirovsky D., Cheng J.D. et al. Clinical outcomes with therapies for previously treated recurrent/metastatic head-and-neck squamous cell carcinoma (R/M HNSCC): a systematic literature review. Oral Oncol 2018;84:108–20. DOI: 10.1016/j.oraloncology.2018.07.005.Ferris R.L., Blumenschein G. Jr, Fayette J. et al. Nivolumab for Recurrent Squamous Cell Carcinoma of the head and neck. N Engl J Med 2016;375:1856–67. DOI: 10.1056/nejmoa1602252.Baxi S.S., Dunn L.A., Burtness B.A. Amidst the excitement: a cautionary tale of immunotherapy, pseudoprogression and head and neck squamous cell carcinoma. Oral Oncol 2016;62:147–8. DOI: 10.1016/j.oraloncology.2016.10.007.Cohen E., Harrington K.J., Le Tourneau C. et al. Pembrolizumab (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):v605–49. DOI: 10.1016/S0140-6736(18)31999-8.Alfieri S., Cavalieri S., Licitra L. Immunotherapy for recurrent/metastatic head and neck cancer. Curr Opin Otolaryngol Head Neck Surg 2018;26(2):152–6. DOI: 10.1097/MOO.0000000000000448.Brower V. Pembrolizumab in advanced head and neck cancer. Lancet Oncol 2017;18(5):e248. DOI: 10.1016/S1470-2045(17)30245-0.Greil R., Rischin D., Harrington K.J. et al. Long-term outcomes from KEYNOTE-048: Pembrolizumab (pembro) alone or with chemotherapy (pembro+C) vs EXTREME (E) as first-line (1L) therapy for recurrent/ metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Ann Oncol 2020;31(S4):S660–1. DOI: 10.1016/j.annonc.2020.08.1030.