Применение ниволумаба при колоректальном раке, ассоциированном с синдромом Линча

1. Burt R. Inheritance of colorectal cancer. Drug Discov Today Dis Mech 2007; 4 (4): 293–300. DOI: 10.1016/j.ddmec.2008.05.004
2. Recommendations from the EGAPP Working Group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives. Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. Genet Med 2009; 11 (1): 35–41.
3. Yurgelun MB, Kulke MH, Fuchs CS et al. Cancer susceptibility gene mutations in individuals with colorectal cancer. J Clin Oncol 2017; 35 (10): 1086–95. DOI: 10.1200/JCO.2016.71.0012
4. Lynch HT, Snyder CL, Shaw TG et al. Milestones of Lynch syndrome: 1895–2015. Nat Rev Cancer 2015; 15: 181–94.
5. Sinicrope FA, Sargent DJ. Clin Cancer Res 2012.
6. NCCN Clinical Practice Guidelines in Oncology (NCCN GuidelinesR) Colon Cancer. Version 2.2019. https:// www.nccn.org/professionals/physician_gls/pdf/colon.pdf
7. Valle L, Vilar E, Tavtigian SV, Stoffel EM. Genetic predisposition to colorectal cancer: syndromes, genes, classification of genetic variants and implications for precision medicine. J Pathol 2019; 247 (5): 574–88. DOI: 10.1002/path.5229
8. Carethers JM, Stoffel EM. Lynch syndrome and Lynch syndrome mimics: the growing complex landscape of hereditary colon cancer. World J Gastroenterol 2015; 21 (31): 9253–61. DOI: 10.3748/wjg.v21.i31.9253
9. Warthin AS. Hereditary with reference to carcinoma. Arch Intern Med (chic) 1913. DOI: 10.1001/archinte.1913.00070050063006
10. Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med 2013. DOI: 10.1056/NEJMra012242
11. Lynch HT. Natural history of colorectal cancer in hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II). Dis Colon Rectum 1988; 31: 439–44. DOI: 10.1007/BF02552613
12. Vasen HF. Screening for hereditary non-polyposis colorectal cancer: a study of 22 kindreds in the Netherlands. Am J Med 1989; 86: 278–81. DOI: 10.1016/0002-9343(89)90296-9
13. Vasen HF. The international collaborative group on hereditary non polyposis colorectal Cancer (ICG-HNPCC). Dis Colon Rectum 1991; 34: 424–5. DOI: 10.1007/BF02053699
14. Lynch HT. Hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II). II Biomarker studies. Cancer 1985; 56: 939–51. DOI: 10.1002/1097-0142(19850815)56:4<939::AID-CNCR2820560440>3.0.CO; 2-T
15. Vasen HF. Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer) J Med Genet 2007; 44: 353–62. DOI: 10.1136/jmg.2007.048991
16. Kastrinos F. Phenotype comparison of MLH1 and MSH2 mutation carriers in a cohort of 1,914 individuals undergoing clinical genetic testing in the United States. Cancer Epidemiol Biomark Prev 2008. DOI: 10.1158/1055-9965
17. Watson P. Extracolonic cancer in hereditary nonpolyposis colorectal cancer. Cancer 1993; 71: 677–85. DOI: 10.1002/1097-0142(19930201)71:3<677::AID-CNCR2820710305>3.0.CO; 2-#
18. Le DT, Durham JN, Smith KN et al. Mismatch repair deficiency predicts response of solid tumors to PD‐1 blockade. Science 2017; 357: 409–13.
19. Venderbosch S, Nagtegaal ID, Maughan TS et al. Mismatch repair statusand BRAF mutation status in metastatic colorectal cancer patients: apooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS studies. Clin Cancer Res 2014; 20 (20): 5322–30.
20. Taieb J, Shi Q, Pederson L et al. Prognosis of microsatellite instability and / or mismatch repair deficiency stage III colon cancer patients after disease recurrence following adjuvant treatment: results of an accent pooled analysis of 7 studies. Ann Oncol 2019. pii: mdz208. DOI: 10.1093/annonc/mdz208
21. Innocenti F, Ou FS, Qu X et al. Mutational Analysis of Patients With Colorectal Cancer in CALGB / SWOG 80405 Identifies New Roles of Microsatellite Instability and Tumor Mutational Burden for Patient Outcome. J Clin Oncol 2019; 37 (14): 1217–27.
22. Yin J, Kong D. Mutation of hMSH3 and hMSH6 mismatch repair genes in genetically unstable human colorectal and gastric carcinomas. Hum Mutat 1997. DOI: 10.1002/(SICI)1098-1004(1997)10:6<474::AID-HUMU9>3.0.CO; 2-D
23. Liu B. hMSH2 mutations in hereditary nonpolyposis colorectal cancer kindreds. Cancer Res 1994; 54: 4590–4.
24. Han HJ. Genomic structure of human mismatch repair gene, hMLH1, and its mutation analysis in patients with hereditary non- polyposis colorectal cancer (HNPCC). Hum Mol Genet 1995; 4: 237–42. DOI: 10.1093/hmg/4.2.237
25. Wijnen J, Khan PM. Hereditary nonpolyposis colorectal cancer families not complying with the Amsterdam criteria show extremely low frequency of mismatch-repair-gene mutations. Am J Hum Genet 1997. DOI: 10.1086/514847
26. Эл. ресурс: https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf
[Available from: https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf (in Russian).]
27. Tiwari AK, Roy HK, Lynch HT. Lynch syndrome in the 21st century: clinical perspectives. QJM 2016; 109 (3): 151–8. DOI: 10.1093/qjmed/hcv137
28. Lichtenstein P, Holm NV, Verkasalo PK et al. Environmental and heritable factors in the causation of cancer. Analyses of cohorts of twins from Sweden, Denmark, and Finland. Engl J Med 2000; 343 (2): 78–85. DOI: 10.1016/S0039-6257 (00)00165-X
29. Yurgelun MB, Kastrinos F. Tumor testing for microsatellite instability to identify Lynch syndrome: new insights into an old diagnostic strategy. J Clin Oncol 2019; 37 (4): 263–5. DOI: 10.1200/JCO.18.01664
30. Bonadona V, Bonaïti B, Olschwang S et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA 2011; 305 (22): 2304–10. DOI: 10.1001/jama.2011.743
31. Møller P, Seppälä T, Bernstein I et al. Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database. Gut 2017; 66 (3): 464–72. DOI: 10.1136/gutjnl-2015-309675
32. Joost P, Therkildsen C, Dominguez-Valentin M et al. Urinary tract cancer in Lynch syndrome; increased risk in carriers of MSH2 mutations. Urology 2015; 86 (6): 1212–7. DOI: 10.1016/j.urology.2015.08.018
33. Kastrinos F, Mukherjee B, Tayob N et al. Risk of pancreatic cancer in families with Lynch syndrome. JAMA 2009; 302 (16): 1790–5. DOI: 10.1001/jama.2009.1529
34. Senter L, Clendenning M, Sotamaa K et al. The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations. Gastroenterology 2008; 135 (2): 419–28.
35. Le DT, Uram JN, Wang H et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015; 372: 2509–20.
36. Study of Pembrolizumab (MK-3475) as Monotherapy in Participants With Previously-Treated Locally Advanced Unresectable or Metastatic Colorectal Cancer (MK-3475-164/KEYNOTE-164). http://clinicaltrials.gov/show/NCT02460198
37. Study of Pembrolizumab (MK-3475) vs Standard Therapy in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Carcinoma (MK-3475-177/KEYNOTE-177). http://clinicaltrials.gov/show/NCT02563002
38. Трякин А.А., Федянин М.Ю., Цуканов А.С. и др. Микросателлитная нестабильность как уникальная характеристика опухолей и предиктор эффективности иммунотерапии. 2019; 9 (4).
[Triakin A.A., Fedianin M.Iu., Tsukanov A.S. et al. Mikrosatellitnaia nestabil'nost' kak unikal'naia kharakteristika opukholei i prediktor effektivnosti immunoterapii. 2019; 9 (4) (in Russian).]
39. Thompson RH, Kuntz SM, Leibovich BC et al. Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-termfollow-up. Cancer Res 2006; 66 (7): 3381–5. DOI: 10.1158/0008–5472.CAN-05–4303. PMID: 16585157
40. Le DT, Uram JN, Wang H et al. PD‐1 blockade in tumors with mismatch‐repair deficiency. N Engl J Med 2015; 372: 2509–20.
41. Eng C, Kim TW, Bendell J et al. Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open‐label, phase 3, randomised, controlled trial. Lancet Oncol 2019; 20 (6): 849–61.
42. Overman MJ, Lonardi S, KYM W et al. Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair‐deficient/microsatellite instability‐high metastatic colorectal cancer. J Clin Oncol 2018; 36 (8): 773–9.
43. Lenz HJ, van Cutsem E, Limon ML et al. Durable clinical benefit with nivolumab (NIVO) plus low‐dose ipilimumab (IPI) as first‐line therapy in microsatellite instability‐high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). Ann Oncol 2018, 29 (8). DOI: 10.1093/annonc/mdy424.019
44. Chalabi M, Fanchi LF, van den Berg JG et al. Neoadjuvant ipilimumab plus nivolumab in early stage colon cancer. Ann Oncol 2018; 29 (Suppl. 8): abstr LBA37.
45. Yarchoan M, Hopkins A, Jaffee EM. Tumor Mutational Burden and Response Rate to PD‐1 Inhibition. N Engl J Med 2017; 377 (25): 2500–1.
46. Samstein R, Lee CH, Shoushtari A et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet 2019; 51: 202–6.
47. Schrock AB, Ouyang C, Sandhu J et al. Tumor mutational burden is predictive of response to immune checkpoint inhibitors in MSI‐high metastatic colorectal cancer. Ann Oncol 2019. pii: mdz134. DOI: 10.1093/annonc/mdz134

________________________________________________

1. Burt R. Inheritance of colorectal cancer. Drug Discov Today Dis Mech 2007; 4 (4): 293–300. DOI: 10.1016/j.ddmec.2008.05.004
2. Recommendations from the EGAPP Working Group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives. Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. Genet Med 2009; 11 (1): 35–41.
3. Yurgelun MB, Kulke MH, Fuchs CS et al. Cancer susceptibility gene mutations in individuals with colorectal cancer. J Clin Oncol 2017; 35 (10): 1086–95. DOI: 10.1200/JCO.2016.71.0012
4. Lynch HT, Snyder CL, Shaw TG et al. Milestones of Lynch syndrome: 1895–2015. Nat Rev Cancer 2015; 15: 181–94.
5. Sinicrope FA, Sargent DJ. Clin Cancer Res 2012.
6. NCCN Clinical Practice Guidelines in Oncology (NCCN GuidelinesR) Colon Cancer. Version 2.2019. https:// www.nccn.org/professionals/physician_gls/pdf/colon.pdf
7. Valle L, Vilar E, Tavtigian SV, Stoffel EM. Genetic predisposition to colorectal cancer: syndromes, genes, classification of genetic variants and implications for precision medicine. J Pathol 2019; 247 (5): 574–88. DOI: 10.1002/path.5229
8. Carethers JM, Stoffel EM. Lynch syndrome and Lynch syndrome mimics: the growing complex landscape of hereditary colon cancer. World J Gastroenterol 2015; 21 (31): 9253–61. DOI: 10.3748/wjg.v21.i31.9253
9. Warthin AS. Hereditary with reference to carcinoma. Arch Intern Med (chic) 1913. DOI: 10.1001/archinte.1913.00070050063006
10. Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med 2013. DOI: 10.1056/NEJMra012242
11. Lynch HT. Natural history of colorectal cancer in hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II). Dis Colon Rectum 1988; 31: 439–44. DOI: 10.1007/BF02552613
12. Vasen HF. Screening for hereditary non-polyposis colorectal cancer: a study of 22 kindreds in the Netherlands. Am J Med 1989; 86: 278–81. DOI: 10.1016/0002-9343(89)90296-9
13. Vasen HF. The international collaborative group on hereditary non polyposis colorectal Cancer (ICG-HNPCC). Dis Colon Rectum 1991; 34: 424–5. DOI: 10.1007/BF02053699
14. Lynch HT. Hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II). II Biomarker studies. Cancer 1985; 56: 939–51. DOI: 10.1002/1097-0142(19850815)56:4<939::AID-CNCR2820560440>3.0.CO; 2-T
15. Vasen HF. Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer) J Med Genet 2007; 44: 353–62. DOI: 10.1136/jmg.2007.048991
16. Kastrinos F. Phenotype comparison of MLH1 and MSH2 mutation carriers in a cohort of 1,914 individuals undergoing clinical genetic testing in the United States. Cancer Epidemiol Biomark Prev 2008. DOI: 10.1158/1055-9965
17. Watson P. Extracolonic cancer in hereditary nonpolyposis colorectal cancer. Cancer 1993; 71: 677–85. DOI: 10.1002/1097-0142(19930201)71:3<677::AID-CNCR2820710305>3.0.CO; 2-#
18. Le DT, Durham JN, Smith KN et al. Mismatch repair deficiency predicts response of solid tumors to PD‐1 blockade. Science 2017; 357: 409–13.
19. Venderbosch S, Nagtegaal ID, Maughan TS et al. Mismatch repair statusand BRAF mutation status in metastatic colorectal cancer patients: apooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS studies. Clin Cancer Res 2014; 20 (20): 5322–30.
20. Taieb J, Shi Q, Pederson L et al. Prognosis of microsatellite instability and / or mismatch repair deficiency stage III colon cancer patients after disease recurrence following adjuvant treatment: results of an accent pooled analysis of 7 studies. Ann Oncol 2019. pii: mdz208. DOI: 10.1093/annonc/mdz208
21. Innocenti F, Ou FS, Qu X et al. Mutational Analysis of Patients With Colorectal Cancer in CALGB / SWOG 80405 Identifies New Roles of Microsatellite Instability and Tumor Mutational Burden for Patient Outcome. J Clin Oncol 2019; 37 (14): 1217–27.
22. Yin J, Kong D. Mutation of hMSH3 and hMSH6 mismatch repair genes in genetically unstable human colorectal and gastric carcinomas. Hum Mutat 1997. DOI: 10.1002/(SICI)1098-1004(1997)10:6<474::AID-HUMU9>3.0.CO; 2-D
23. Liu B. hMSH2 mutations in hereditary nonpolyposis colorectal cancer kindreds. Cancer Res 1994; 54: 4590–4.
24. Han HJ. Genomic structure of human mismatch repair gene, hMLH1, and its mutation analysis in patients with hereditary non- polyposis colorectal cancer (HNPCC). Hum Mol Genet 1995; 4: 237–42. DOI: 10.1093/hmg/4.2.237
25. Wijnen J, Khan PM. Hereditary nonpolyposis colorectal cancer families not complying with the Amsterdam criteria show extremely low frequency of mismatch-repair-gene mutations. Am J Hum Genet 1997. DOI: 10.1086/514847
26. Available from: https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf (in Russian).
27. Tiwari AK, Roy HK, Lynch HT. Lynch syndrome in the 21st century: clinical perspectives. QJM 2016; 109 (3): 151–8. DOI: 10.1093/qjmed/hcv137
28. Lichtenstein P, Holm NV, Verkasalo PK et al. Environmental and heritable factors in the causation of cancer. Analyses of cohorts of twins from Sweden, Denmark, and Finland. Engl J Med 2000; 343 (2): 78–85. DOI: 10.1016/S0039-6257 (00)00165-X
29. Yurgelun MB, Kastrinos F. Tumor testing for microsatellite instability to identify Lynch syndrome: new insights into an old diagnostic strategy. J Clin Oncol 2019; 37 (4): 263–5. DOI: 10.1200/JCO.18.01664
30. Bonadona V, Bonaïti B, Olschwang S et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA 2011; 305 (22): 2304–10. DOI: 10.1001/jama.2011.743
31. Møller P, Seppälä T, Bernstein I et al. Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database. Gut 2017; 66 (3): 464–72. DOI: 10.1136/gutjnl-2015-309675
32. Joost P, Therkildsen C, Dominguez-Valentin M et al. Urinary tract cancer in Lynch syndrome; increased risk in carriers of MSH2 mutations. Urology 2015; 86 (6): 1212–7. DOI: 10.1016/j.urology.2015.08.018
33. Kastrinos F, Mukherjee B, Tayob N et al. Risk of pancreatic cancer in families with Lynch syndrome. JAMA 2009; 302 (16): 1790–5. DOI: 10.1001/jama.2009.1529
34. Senter L, Clendenning M, Sotamaa K et al. The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations. Gastroenterology 2008; 135 (2): 419–28.
35. Le DT, Uram JN, Wang H et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015; 372: 2509–20.
36. Study of Pembrolizumab (MK-3475) as Monotherapy in Participants With Previously-Treated Locally Advanced Unresectable or Metastatic Colorectal Cancer (MK-3475-164/KEYNOTE-164). http://clinicaltrials.gov/show/NCT02460198
37. Study of Pembrolizumab (MK-3475) vs Standard Therapy in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Carcinoma (MK-3475-177/KEYNOTE-177). http://clinicaltrials.gov/show/NCT02563002
38. Triakin A.A., Fedianin M.Iu., Tsukanov A.S. et al. Mikrosatellitnaia nestabil'nost' kak unikal'naia kharakteristika opukholei i prediktor effektivnosti immunoterapii. 2019; 9 (4) (in Russian).
39. Thompson RH, Kuntz SM, Leibovich BC et al. Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-termfollow-up. Cancer Res 2006; 66 (7): 3381–5. DOI: 10.1158/0008–5472.CAN-05–4303. PMID: 16585157
40. Le DT, Uram JN, Wang H et al. PD‐1 blockade in tumors with mismatch‐repair deficiency. N Engl J Med 2015; 372: 2509–20.
41. Eng C, Kim TW, Bendell J et al. Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open‐label, phase 3, randomised, controlled trial. Lancet Oncol 2019; 20 (6): 849–61.
42. Overman MJ, Lonardi S, KYM W et al. Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair‐deficient/microsatellite instability‐high metastatic colorectal cancer. J Clin Oncol 2018; 36 (8): 773–9.
43. Lenz HJ, van Cutsem E, Limon ML et al. Durable clinical benefit with nivolumab (NIVO) plus low‐dose ipilimumab (IPI) as first‐line therapy in microsatellite instability‐high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). Ann Oncol 2018, 29 (8). DOI: 10.1093/annonc/mdy424.019
44. Chalabi M, Fanchi LF, van den Berg JG et al. Neoadjuvant ipilimumab plus nivolumab in early stage colon cancer. Ann Oncol 2018; 29 (Suppl. 8): abstr LBA37.
45. Yarchoan M, Hopkins A, Jaffee EM. Tumor Mutational Burden and Response Rate to PD‐1 Inhibition. N Engl J Med 2017; 377 (25): 2500–1.
46. Samstein R, Lee CH, Shoushtari A et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet 2019; 51: 202–6.
47. Schrock AB, Ouyang C, Sandhu J et al. Tumor mutational burden is predictive of response to immune checkpoint inhibitors in MSI‐high metastatic colorectal cancer. Ann Oncol 2019. pii: mdz134. DOI: 10.1093/annonc/mdz134

Г.А. Хакимов1,2, А.А. Трякин3,4, Г.Г. Хакимова*3

1 Ташкентский педиатрический медицинский институт, Ташкент, Республика Узбекистан;
2 Ташкентский городской филиал Республиканского специализированного научно-практического медицинского центра онкологии и радиологии Минздрава Республики Узбекистан, Ташкент, Республика Узбекистан;
3 ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России, Москва, Россия;
4 ГБУЗ «Московский клинический научно-практический центр им. А.С. Логинова» Департамента здравоохранения г. Москвы, Москва, Россия
*hgg_doc@mail.ru

________________________________________________

Golib A. Khakimov1,2, Alexey A. Tryakin3,4, Gulnoz G. Khakimova*3

1 Tashkent Pediatric Medical Institute, Republic of Uzbekistan;
2 Tashkent City branch Republican Specialized Scientific-Practical Medical Center of Oncology and Radiology, Tashkent, Republic of Uzbekistan;
3 Blokhin National Medical Research Center of Oncology, Moscow, Russia;
4 Loginov Moscow Clinical Scientific Center, Moscow, Russia
*hgg_doc@mail.ru