Preview

Медицинский алфавит

Расширенный поиск
Доступ открыт Открытый доступ  Доступ закрыт Доступ платный или только для Подписчиков

Иммунотерапия при местнораспространенном, рецидивном и метастатическом раке головы и шеи: последние достижения и будущие направления

https://doi.org/10.33667/2078-5631-2020-20-60-69

Полный текст:

Аннотация

Три рандомизированных исследования III фазы в настоящее время убедительно доказали, что применение ингибиторов PD-I увеличивает общую выживаемость при рецидивирующей / метастатической форме (Р/М) плоскоклеточного рака головы и шеи, и что данные препараты должны использоваться в лечении всех пациентов, у которых нет противопоказаний к их применению. Два из этих рандомизированных исследований показали, что антиPD-1-антитела ниволумаб и пембролизумаб превосходят по эффективности терапию по выбору исследователя во второй линии терапии при платинорезистентном Р/M плоскоклеточном раке головы и шеи. Третье рандомизированное исследование III фазы, KEYNOTE-048, показало, что пембролизумаб в комбинации с химиотерапией превосходит по эффективностирежим EXTREME(цис- или карбоплатин, 5-фторурацил [5-Ф] и цетуксимаб) у всех пациентов независимо от экспрессии PD-L1, а монотерапия пембролизумабом, по сравнению с режимом EXTREME, достоверно увеличивает показатели ОВ у пациентов, у которых опухоли экспрессируют PD-L1 в первой линии терапии при Р/M плоскоклеточном раке головы и шеи. Пембролизумаб в настоящее время одобрен Управлением по санитарному контролю за продуктами и медикаментами США в первой линии в качестве монотерапии при наличии экспрессии PD-L1 (CPS≥ 1) или в комбинации с химиотерапией независимо от статуса PD-L1. Таким образом, тестирование биомаркера PD-L1 с использованием комбинированного показателя позитивности (CPS) будет использоваться при Р/M плоскоклеточном раке головы и шеи. Кроме того, для 85 % пациентов с экспрессией PD-L1 (CPS≥ 1) клинически будет необходимо определять выбор между монотерапией пембролизумабом или пембролизумабом в комбинации c химиотерапией до тех пор, пока не появятся более дополнительные клинические данные. В статье обсуждаются клинические исследования, которые привели к этим терапевтическим достижениям. Рассмотрены предварительные результаты клинических исследований при ранее не леченном местнораспространенном раке и те, в которых оцениваются новые комбинации ингибиторов иммунных контрольных точек, костимулирующих агонистов и терапевтических вакцин.

Об авторах

З. А.-Г. Раджабова
ФГБУ «Национальный медицинский исследовательский центр онкологии имени Н.Н. Петрова» Минздрава России
Россия

Кандидат медицинских наук, зав. хирургическим отделением опухолей головы и шеи

Санкт-Петербург


М. А. Котов
ФГБУ «Национальный медицинский исследовательский центр онкологии имени Н.Н. Петрова» Минздрава России
Россия

Врач-онколог хирургического отделения опухолей головы и шеи.

Санкт-Петербург



А. С. Митрофанов
ФГБУ «Национальный медицинский исследовательский центр онкологии имени Н.Н. Петрова» Минздрава России
Россия

Ординатор хирургического отделения опухолей головы и шеи.

Санкт-Петербург



З. С. Бекяшева
ФГБУ «Национальный медицинский исследовательский центр онкологии имени Н.Н. Петрова» Минздрава России
Россия

Ординатор хирургического отделения опухолей головы и шеи.

Санкт-Петербург



Е. В. Левченко
ФГБУ «Национальный медицинский исследовательский центр онкологии имени Н.Н. Петрова» Минздрава России
Россия

Доктор медицинских наук, член-корр. РАН, зав. хирургическим отделением торакальной онкологии.

Санкт-Петербург



Список литературы

1. Bray F, Ferlay J, Soerjomafaram 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: 394-424.

2. Leemans CR, Braakhuis BJ, Brakenhoff RH. The molecular biology of head and neck cancer. Nat Rev Cancer2011; 11: 9-22.

3. Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008; 359: 1116-27.

4. Lawrence MS, Stojanov P, Polak P, et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 2013; 499:214-8.

5. Rizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 2015; 348: 124-8.

6. Cannataro VL, Gaffney SG, Sasaki T, et al. APO-BEC-induced mutations and their cancer effect size in head and neck squamous cell carcinoma. Oncogene 2019; 38: 3475-87.

7. Pan C, Issaeva N, Yarbrough WG. HPV-driven oropharyngeal cancer: current knowledge of molecular biology and mechanisms of carcinogenesis. Cancers Head Neck2018; 3: 12.

8. Boichard A, Pham TV, Yeerna H, et al. APOBEC-re-lated mutagenesis and neo-peptide hydrophobic-ity: implications for response to immunotherapy. Oncoimmunology 2019; 8: 1550341.

9. Cottin SC, Turcotte S, Douville P, et al. Predictors of circulating interleukin-6 levels in head and neck cancer patients. Cancers Head Neck2018: 3.

10. Whiteside TL. Immune cells in the tumor microenvironment. Mechanisms responsible for functional and signaling defects. Adv Exp Med Biol 1998; 451: 167-71.

11. Bauernhofer T, Kuss I, Henderson B, et al. Preferential apoptosis of CD56 dim natural killer cell subset in patients with cancer. Eur J Immunol 2003; 33: 119-24.

12. Ferris RL, Whiteside TL, Ferrone S. Immune escape associated with functional defects in antigen-processing machinery in head and neck cancer. Clin Cancer Res 2006; 12: 3890-5.

13. Ferris RL. Immunology and immunotherapy of head and neck cancer. J Clin Oncol 2015; 33: 3293-304.

14. 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.

15. Lala M, Chirovsky D, Cheng JD, et al. Clinical outcomes with therapies for previously treated re-current/metastatic head-and-necksquamous cell carcinoma (R/M HNSCC): a systematic literature review. Oral Oncol 2018; 84: 108-20.

16. 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: 956-65.

17. Mehra R, Seiwert TY, Gupta S, et al. Effcacy 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 Cancer2018; 119: 153-9.

18. Ferris RL, Blumenschein Jr. G, Fayette J, et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the head and neck. N Engl J Med 2016; 375: 1856-67.

19. Bauml J, Seiwert TY, Pfister DG, 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: 1542-9.

20. Cohen EEW, Soulieres D, Le Tourneau C, et al. Pem-brolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet 2019; 393: 156-67.

21. Cohen E, Harrington K, Tourneau C, et al. Pem-brolizumab (pembro) vs standard of care (SOC) for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC): phase 3 KEYNOTE-040 trial. Madrid, Spain: European Society of Medical Oncology; 2017.

22. Ferris RL, Blumenschein Jr. G, Fayette J, et al. Nivolumab vs investigator’s choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long-term survival update of CheckMate 141 with analyses by tumor PD-L1 expression. Oral Oncol 2018; 81: 45-51.

23. EisenhauerEA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45(2): 228-47. https://doi.org/10.1016/j.ejca.2008.10.026.

24. Baxi SS, Dunn LA, Burtness BA. Amidst the excitement: a cautionary ta/e of immunotherapy, pseudoprogression and head and neck squamous cell carcinoma. Oral Oncol 2016; 62: 147-8.

25. Haddad R, Concha-Benavente F, Blumenschein Jr G, et al. Nivolumab treatment beyond RECIST-defined progression in recurrent or metastatic squamous cell carcinoma of the head and neck in CheckMate 141: a subgroup analysis of a randomized phase 3 clinical trial. Cancer2019.

26. Champiat S, Dercle L, Ammari S, et al. Hyperprogressive Disease is a new pattern of progression in cancer patients treated by anti-PD-1/PD-L1. Clin Cancer Res 2017; 23: 1920-8.

27. Saada-Bouzid E, Defaucheux C, Karabajakian A, et al. Hyperprogression during anti- PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Ann Oncol 2017; 28: 1605-11.

28. Xiang JJ, Uy NF, Minja FJ, et al. Hyperprogression after one dose of nivolumab in sinonasal cancer, a case report. Laryngoscope 2019.

29. Harrington KJ, Ferris RL, Blumenschein Jr G, 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: 1104-15.

30. Cohen EEW, Soulieres D, Le Tourneau C, et al. Pem-brolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet 2018.

31. Cohen EEW, Soulieres D, Tourneau CL, et al. Health-related quality of life (HRQoL) of pem-brolizumab (pembro) vs standard of care (SOC) for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) in KEYNOTE-040. J Clin Oncol 2018; 36. 6013-6013.

32. Rischin D, Harrington KJ, Greil R, et al. Protocol-specified final analysis of the phase 3 KEYNOTE-048 trial of pembrolizumab (pembro) as first-line therapy for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). J Clin Oncol 2019; 37. 6000-6000.

33. Burtness B, Harrington K, Greil R, et al. KEYNOTE-048: Phase III study of first-line pembrolizumab (P) for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Germany: European Society of Medical Oncology. Munich; 2018.

34. 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.

35. Chow LQ, Burtness B, Weiss J, et al. LBA31A phase IB study of pembrolizumab (Pembro; MK-3475) in patients (PTS) with human papiilloma virus (HPV)-positive and negative head and neck cancer (HNC). Ann Oncol 2014; 25.

36. Roach C, Zhang N, Corigliano E, et al. Development of a Companion Diagnostic PD-L1 Immuno-histochemistry assay for pembrolizumab therapy in non-small-cell lung cancer. Appl Immunohisto-chem Mol Morphol 2016; 24: 392-7.

37. Cohen EEW, Bell RB, Bifulco CB, 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 Cancer2019; 7: 184.

38. Concha-Benavente F, Srivastava RM, Trivedi S, et al. Identification of the cell-intrinsic and extrinsic pathways downstream of EGFR and IFNgamma that induce PD-L1 expression in head and neck cancer. Cancer Res 2016; 76: 1031-43.

39. Ferris RL, Blumenschein G, Harrington K, et al. Abstract CT021: tumor-associated immune cell PD-L1 expressio n and peripheral immune pro filing: analyses from CheckMate 141. Cancer Res 2017; 77. CTU21-CTU21.

40. Yearley JH, Gibson C, Yu N, et al. PD-L2 expression in human tumors: relevance to anti-PD-1 therapy in cancer. Clin Cancer Res 2017; 23: 3158-67.

41. Ratcliffe MJ, Sharpe A, Midha A, et al. Agreement between Programmed Cell Death Ligand-1 diagnostic assays across multiple protein expression cutoffs in non-small cell lung cancer. Clin Cancer Res 2017; 23: 3585-91.

42. Tsao MS, Kerr KM, Kockx M, et al. PD-L1 immunohis-tochemistry comparability study in real-life clinical samples: results of blueprint phase 2 project. J Thorac Oncol 2018; 13: 1302-11.

43. Chow LQM, 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: 3838-45.

44. Gameiro SF, Ghasemi F, Barrett JW, et al. Treatment-naive HPV+ head and neck cancers display a T-cell-inflamed phenotype distiNCTfrom their HPV- counterparts that has implications for immunotherapy. Oncoimmunology 2018; 7: e1498439.

45. 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 Oncol2005; 23:8646-54.

46. MassarelliE, William W, Johnson F, et al. Combining immune checkpoint blockade and tumor-specific vaccine for patients with incurable human papillomavirus 16-related cancer: a phase 2 clinical trial. JAMA Oncol 2019; 5: 67-73.

47. Aggarwal C, Cohen RB, Morrow MP, et al. Immunotherapy targeting HPV16/18 generates potent immune responses in HPV-associated head and neck cancer. Clin Cancer Res 2019; 25: 110-24.

48. Prat A, Navarro A, Pare L, et al. Immune-Related Gene Expression Profiling After PD-1 Blockade in Non-Small Cell Lung Carcinoma, Head and Neck Squamous Cell Carcinoma, and Melanoma. Cancer Res 2017; 77: 3540-50.

49. Ferris RL, Licitra L, Fayette J, et al. Nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: effcacy and safety in CheckMate 141 by Prior cetuximab use. Clin Cancer Res 2019.

50. Le Tourneau C, Cohen EE, Harrington KJ, et al. Pembrolizumab for recurrent head and neck squamous cell carcinoma (HNSCC): post-hoc analyses of treatment options from the phase 3 KEYNOTE-040 trial. Germany: European Society for Medical Oncology. Munich; 2018.

51. Argiris A, Li Y, Murphy BA, et al. Outcome of elderly patients with recurrent or metastatic head and neck cancer treated with cisplatin-based chemotherapy. J Clin Oncol 2004; 22: 262-8.

52. Saba NF, Blumenschein GR, Guigay J, et al. Nivolumab (nivo) vs investigator’s choice (IC) in patients (pts) with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): analysis of CheckMate 141 by age. J Clin Oncol 2018; 36. 6028-6028.

53. Spano JP, Veyr M, Gobert A, et al. Immunotherapy for cancer in people living with HIV: safety with an effcacy signal from the series in real life experience. AIDS 2019; 33: F13-9.

54. Abdel-Wahab N, Safa H, Abudayyeh A, et al. Checkpoint inhibitor therapy for cancer in solid organ transplantation recipients: an institutional experience and a systematic review of the literature. J ImmunoTher Cancer2019; 7: 106.

55. Segal NS, Ou SH, Balmanoukian AS, et al. Safety and effcacy of MEDI4736, an anti-PD-L1 antibody, in patients from a squamous cell carcinoma of the head and neck (SCCHN) expansion cohort. J Clin Oncol 2015; 33. 3011-3011.

56. Licitra LF, Haddad RI, Even C, et al. EAGLE: a phase 3, randomized, open-label study of durvalumab (D) with or without tremelimumab (T) in patients (pts) with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). J Clin Oncol 2019; 37. 6012-6012.

57. Siu LL, Even C, Mesia R, et al. Safety and effcacy of durvalumab with or without tremelimumab in patients with PD-L1-low/negative recurrent or metastatic HNSCC: the phase 2 CONDOR randomized clinical trial. JAMA Oncol 2018.

58. PardollDM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012; 12: 252-64.

59. Wolchok JD, Kluger H, Callahan MK, et al. Nivolum-ab plus ipilimumab in advanced melanoma. N Engl J Med 2013; 369: 122-33.

60. Sqibb B-M. Bristol-Myers Squibb reports first quarter financial results; 2019.

61. Uppaluri R, Zolkind P, Lin T, et al. Neoadjuvant pembrolizumab in surgically resectable, locally advanced HPV negative head and neck squamous cellcarcinoma (HNSCC). J Clin Oncol2017; 35:6012.

62. Ferrarotto R, Bell D, Rubin ML, et al. Checkpoint inhibitors assessment in oropharynx cancer (CIAO): safety and interim results. J Clin Oncol2019; 37. 6008-6008.

63. Horton JD, Knochelmann H, Armeson K, et al. Neoadjuvant presurgical PD-1 inhibition in oral cavity squamous cell carcinoma. J Clin Oncol 2019; 37. 2574-2574.

64. Hamid O, Bauer TM, Spira AI, et al. Epacadostat plus pembrolizumab in patients with SCCHN: preliminary phase I/II results from ECHO-202/KEY-NOTE-037. J Clin Oncol 2017; 35. 6010-6010.

65. Ferris RL, Saba NF, Gitlilz BJ, et al. Effect of adding motolimod to standard combination chemotherapy and cetuximab treatment of patients with squamous cell carcinoma of the head and neck: the active8 randomized clinical trial. JAMA Oncol2018; 4:1583-8.

66. Cohen E, Bishnoi S, Laux DE, et al. Abstract CT098: phase Ib/II, open label, multicenterstudy of intratu-moralSD-101 in combination with pembrolizumab in anti-PD-1 treatment naive patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Cancer Res 2018; 78. C1098-CT098.

67. Massarelli E, William W, Johnson F, et al. Combining immune checkpoint blockade and tumor-specific vaccine for patients with incurable human papillomavirus 16-related cancer: a phase 2 clinical trial. JAMA Oncol 2018.

68. Schuler PJ, Harasymczuk M, Visus C, et al. Phase I dendritic cell p53 peptide vaccine for head and neck cancer. Clin Cancer Res 2014; 20:2433-44.

69. Harrington KJ, Hingorani M, Tanay MA, et al. Phase I/II study of oncolytic HSV GM-CSF in combination with radiotherapy and cisplatin in untreated stage III/IV squamous cell cancer of the head and neck. Clin Cancer Res 2010; 16: 4005-15.

70. Sacco AG, Chen R, Ghosh D, et al. An open label, nonrandomized, multi-arm, phase II trial evaluating pembrolizumab combined with cetuximab in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): results of cohort I interim analysis. J Clin Oncol2019; 37. 6033-6033.

71. TaylorMH, Rasco DW, Brose MS, et al. A phase 1b/2 trial of envatinib plus pembrolizumab in patients with squamous cell arcinoma of the head and neck. J Clin Oncol 2018; 36. 6016-6016.

72. Davis RJ, Ferris RL, Schmitt NC. Costimulatory and coinhibitory immune checkpoint receptors in head and neck cancer: unleashing immune responses through therapeutic combinations. Cancers of the Head Neck2016; 1: 12.

73. Demaria S, Kawashima N, Yang AM, et al. Im-mune-mediated inhibition of metastases after treatment with local radiation and CTLA-4 blockade in a mouse model of breast cancer. Clin Cancer Res 2005; 11: 728-34.

74. McBride SM, Sherman EJ, Tsai CJ, et al. A phase II randomized trial of nivolumab with stereotactic body radiotherapy (SBRT) versus nivolumab alone in metastatic (M1) head and neck squamous cell carcinoma (HNSCC). J Clin Oncol 2018; 36.

75. Bauman JE, Harris J, Uppaluri R, et al. NRG-HN 003: phase I and expansion cohort study of adjuvant cisplatin, intensity-modulated radiation therapy (IMRT), and MK-3475 (Pembrolizumab) in high-risk head and neck squamous cell carcinoma (HN-SCC). J Clin Oncol 2019; 37. 6023-6023.

76. Sun XS, Sire C, Tao Y, et al. A phase II randomized trial of pembrolizumab versus cetuximab, concomitant with radiotherapy (RT) in locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN): first results of the GORTEC2015-01 ‘PembroRad’ trial. J Clin Oncol2018; 36.6018-6018.

77. Ferris RL, Gillison ML, Harris J, et al. Safety evaluation of nivolumab (Nivo) concomitant with cetuximab-radiotherapy for intermediate (IR) and high-risk (HR) local-regionally advanced head and neck squamous cell carcinoma (HNSCC): RTOG 3504. J Clin Oncol 2018; 36. 6010-6010.


Для цитирования:


Раджабова З.А., Котов М.А., Митрофанов А.С., Бекяшева З.С., Левченко Е.В. Иммунотерапия при местнораспространенном, рецидивном и метастатическом раке головы и шеи: последние достижения и будущие направления. Медицинский алфавит. 2020;(20):60-69. https://doi.org/10.33667/2078-5631-2020-20-60-69

For citation:


Radzhabova Z.A., Kotov M.Д., Mitrofanov A.S., Bekyasheva Z.S., Levchenko E.V. Immunotherapy for regional, recurrent and metastatic head and neck cancer: recent advances and future directions. Medical alphabet. 2020;(20):60-69. (In Russ.) https://doi.org/10.33667/2078-5631-2020-20-60-69

Просмотров: 154


ISSN 2078-5631 (Print)