1. Каприн А.Д., Старинский В.В. и др. Состояние онкологической помощи населению России в 2014 году. М., 2015. / Kaprin A.D., Starinskii V.V. i dr. Sostoianie onkologicheskoi pomoshchi naseleniiu Rossii v 2014 godu. M., 2015. [in Russian]
2. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. Non-small cell Lung Cancer Collaborative Group. BMJ 1995; 311: 889–909.
3. Ciuleanu T et al. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet 2009; 374: 1432–40.
4. Schiller JH et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N. Engl J Med 2002; 346: 92–8.
5. Sandler A et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006; 355: 2542–50.
6. Scagliotti G et al. The differential efficacy of pemetrexed according to NSCLC histology: a review of two Phase III studies. Oncologist 2009; 14: 253–63.
7. Fukuoka M et al. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol 2011; 29: 2866–74.
8. Reck M et al. Management of non-small-cell lung cancer: recent developments. Lancet 2013; 382: 709–19.
9. Cheng L et al. Molecular pathology of lung cancer: key to personalized medicine. Mod Pathol 2012; 25: 347–69.
10. Harris TJ, McCormick F. The molecular pathology of cancer. Nat Rev Clin Oncol 2010; 7: 251–65.
11. Seshacharyulu P et al. Targeting the EGFR signaling pathway in cancer therapy. Expert Opin Ther Targets 2012; 16: 15–31.
12. Yarden Y et al. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2001; 2: 127–37.
13. Baselga J et al. Epithelial growth factor receptor interacting agents. Hematol Oncol Clin North Am 2002; 16: 1041–63.
14. Herbst RS et al. ZD1839: targeting the epidermal growth factor receptor in cancer therapy. Expert Opin Invest Drugs 2002; 11: 837–49.
15. Arteaga CL. EGF receptor mutations in lung cancer: from humans to mice and maybe back to humans. Cancer Cell 2006; 9: 421–3.
16. Gazdar AF et al. Mutations and addiction to EGFR: the Achilles 'heal' of lung cancers? Trends Mol Med 2004; 10: 481–6.
17. Hendricks BS et al. Decreased internalisation of erbB1 mutants in lung cancer is linked with a mechanism conferring sensitivity to gefitinib. Systems Biology 2006; 153: 457–66.
18. Sordella R et al. Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science 2004; 305: 1163–7.
19. Tjulandin S et al. Prospective cohort study of clinical characteristics and management patterns for patients with non-small-cell lung cancer in the Russian Federation: EPICLIN-Lung. Curr Med Res Opin 2015; 31 (6): 1117–27.
20. Sharma SV et al. Epidermal growth factor receptor mutations in lung cancer. Nature Rev Cancer 2007; 7: 169–81.
21. Rosell R et al. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 2009; 361 (10): 958–67.
22. Mok TS et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947–57.
23. Моисеенко В.М., Проценко С.А., Семенов И.И. Применение Ирессы (гефитиниба) в качестве терапии первой линии для лечения неоперабельных аденокарцином легкого, содержащих мутацию в гене EGFR. Современная Онкология. 2010; 12 (1): 60–6. / Moiseenko V.M., Protsenko S.A., Semenov I.I. Primenenie Iressy (gefitiniba) v kachestve terapii pervoi linii dlia lecheniia neoperabel'nykh adenokartsinom legkogo, soderzhashchikh mutatsiiu v gene EGFR. Journal of Modern Oncology. 2010; 12 (1): 60–6. [in Russian]
24. Stewart EL et al. Known and putative mechanisms of resistance to EGFR targeted therapies in NSCLC patients with EGFR mutations – a review. Transl Lung Cancer Res 2015; 4 (1): 67–81.
25. Практические рекомендации по лечению злокачественных опухолей. URL: http://www.rosoncoweb.ru/standarts/RUSSCO/ 01.pdf / Prakticheskie rekomendatsii po lecheniiu zlokachestvennykh opukholei. URL: http://www.rosoncoweb.ru/standarts/RUSSCO/01.pdf [in Russian]
26. NCCN Guidelines. URL: http://www.nccn.org/ professionals/ physician gls/pdf/nscl.pdf
27. Reck M. et al. Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2014; 25 (Suppl. 3): iii27–39.
28. Leighl NB et al. Molecular testing for selection of patients with lung cancer for epidermal growth factor receptor and anaplastic lymphoma kinase tyrosine kinase inhibitors: American Society of Clinical Oncology endorsement of the College of American Pathologists/International Association for the study of lung cancer/association for molecular pathology guideline. J Clin Oncol 2014; 32 (32): 3673–9.
29. Горбунова В.А., Артамонова Е.В., Бредер В.В. и др. Практические рекомендации по лекарственному лечению немелкоклеточного рака легкого. Злокачественные опухоли. 2016; 4. (Спецвып. 2): 22–33. / Gorbunova V.A., Artamonova E.V., Breder V.V. i dr. Prakticheskie rekomendatsii po lekarstvennomu lecheniiu nemelkokletochnogo raka legkogo. Zlokachestvennye opukholi. 2016; 4. (Spetsvyp. 2): 22–33. [in Russian]
30. Johnson BE et al. A multicenter effort to identify driver mutations and employ targeted therapy in patients with lung adenocarcinomas: The Lung Cancer Mutation Consortium (LCMC). J Clin Oncol 2013; 31 (Suppl.): abstr. 8019.
31. Maemondo M et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010; 362: 2380–8.
32. Mitsudomi T et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 2010; 11: 121–8.
33. Lin JJ et al. Five-Year Survival in EGFR-Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs.  J Thorac Oncol 2016; 11 (4): 556–65.
34. Scagliotti GV et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 2008; 26: 3543–51.
35. Zhang L et al. Gefitinib versus placebo as maintenance therapy in patients with locally advanced or metastatic non-small-cell lung cancer (INFORM; C-TONG 0804): a multicentre, double-blind randomised phase 3 trial. Lancet Oncol 2012; 13 (5): 466–75.
36. Burotto M et al. Gefitinib and erlotinib in metastatic non-small cell lung cancer: a meta-analysis of toxicity and efficacy of randomized clinical trials. Oncologist 2015; 20: 400–10.
37. Park K et al. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol 2016; 17: 577–89.
38. Park K et al. First-Line Erlotinib Therapy Until and Beyond Response Evaluation Criteria in Solid Tumors Progression in Asian Patients With Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer: The ASPIRATION Study. JAMA Oncol 2016; 2 (3): 305–12.
39. Weickhardt AJ et al. Local ablative therapy of oligoprogressive disease prolongs disease control by tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer. J Thorac Oncol 2012; 7 (12): 1807–14.
40. Cortot AB, Jänne PA. Molecular mechanisms of resistance in epidermal growth factor receptor-mutant lung adenocarcinomas. Eur Respir Rev 2014; 23 (133): 356–66.
41. Jackman D et al. Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. J Clin Oncol 2010; 28 (2): 357–60.
42. Yu HA et al. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin Cancer Res 2013; 19: 2240–7.
43. Oxnard GR et al. Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: distinct natural history of patients with tumors harboring the T790M mutation. Clin Cancer Res 2011; 17 (6): 1616–22.
44. Sun JM et al. Clinical implications of T790M mutation in patients with acquired resistance to EGFR tyrosine kinase inhibitors. Lung Cancer 2013; 82: 294–8.
45. Kuiper JL et al. Incidence of T790M mutation in (sequential) rebiopsies in EGFR-mutated NSCLC-patients. Lung Cancer 2014; 85: 19–24.
46. Li W et al. T790M mutation is associated with better efficacy of treatment beyond progression with EGFR-TKI in advanced NSCLC patients. Lung Cancer 2014; 84: 295–300.
47. Kobayashi S et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 2005; 352: 786–92.
48. Cross DA et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov 2014; 4: 1046–61.
49. Yun CH et al. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci USA 2008; 105: 2070–5.
50. Kris MG et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA 2014; 311 (19): 1998–2006.
51. Fukuoka M et al. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial) [corrected]. J Clin Oncol 2003; 21 (12): 2237–46.
52. Kris MG et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA 2003; 290: 2149–58.
53. Mok T, Yang JJ, Lam KC. Treating patients with EGFR-sensitizing mutations: first line or second line--is there a difference? J Clin Oncol 2013; 31 (8): 1081–8.
54. Park K. LUX-Lung 7: is there enough data for a final conclusion? Lancet Oncol 2016; 17 (7): e268-9.
55. Sequist LV et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 2013; 31 (27): 3327–34.

________________________________________________

1. Kaprin A.D., Starinskii V.V. i dr. Sostoianie onkologicheskoi pomoshchi naseleniiu Rossii v 2014 godu. M., 2015. [in Russian]
2. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. Non-small cell Lung Cancer Collaborative Group. BMJ 1995; 311: 889–909.
3. Ciuleanu T et al. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet 2009; 374: 1432–40.
4. Schiller JH et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N. Engl J Med 2002; 346: 92–8.
5. Sandler A et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006; 355: 2542–50.
6. Scagliotti G et al. The differential efficacy of pemetrexed according to NSCLC histology: a review of two Phase III studies. Oncologist 2009; 14: 253–63.
7. Fukuoka M et al. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol 2011; 29: 2866–74.
8. Reck M et al. Management of non-small-cell lung cancer: recent developments. Lancet 2013; 382: 709–19.
9. Cheng L et al. Molecular pathology of lung cancer: key to personalized medicine. Mod Pathol 2012; 25: 347–69.
10. Harris TJ, McCormick F. The molecular pathology of cancer. Nat Rev Clin Oncol 2010; 7: 251–65.
11. Seshacharyulu P et al. Targeting the EGFR signaling pathway in cancer therapy. Expert Opin Ther Targets 2012; 16: 15–31.
12. Yarden Y et al. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2001; 2: 127–37.
13. Baselga J et al. Epithelial growth factor receptor interacting agents. Hematol Oncol Clin North Am 2002; 16: 1041–63.
14. Herbst RS et al. ZD1839: targeting the epidermal growth factor receptor in cancer therapy. Expert Opin Invest Drugs 2002; 11: 837–49.
15. Arteaga CL. EGF receptor mutations in lung cancer: from humans to mice and maybe back to humans. Cancer Cell 2006; 9: 421–3.
16. Gazdar AF et al. Mutations and addiction to EGFR: the Achilles 'heal' of lung cancers? Trends Mol Med 2004; 10: 481–6.
17. Hendricks BS et al. Decreased internalisation of erbB1 mutants in lung cancer is linked with a mechanism conferring sensitivity to gefitinib. Systems Biology 2006; 153: 457–66.
18. Sordella R et al. Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science 2004; 305: 1163–7.
19. Tjulandin S et al. Prospective cohort study of clinical characteristics and management patterns for patients with non-small-cell lung cancer in the Russian Federation: EPICLIN-Lung. Curr Med Res Opin 2015; 31 (6): 1117–27.
20. Sharma SV et al. Epidermal growth factor receptor mutations in lung cancer. Nature Rev Cancer 2007; 7: 169–81.
21. Rosell R et al. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 2009; 361 (10): 958–67.
22. Mok TS et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947–57.
23. Moiseenko V.M., Protsenko S.A., Semenov I.I. Primenenie Iressy (gefitiniba) v kachestve terapii pervoi linii dlia lecheniia neoperabel'nykh adenokartsinom legkogo, soderzhashchikh mutatsiiu v gene EGFR. Journal of Modern Oncology. 2010; 12 (1): 60–6. [in Russian]
24. Stewart EL et al. Known and putative mechanisms of resistance to EGFR targeted therapies in NSCLC patients with EGFR mutations – a review. Transl Lung Cancer Res 2015; 4 (1): 67–81.
25. Prakticheskie rekomendatsii po lecheniiu zlokachestvennykh opukholei. URL: http://www.rosoncoweb.ru/standarts/RUSSCO/01.pdf [in Russian]
26. NCCN Guidelines. URL: http://www.nccn.org/ professionals/ physician gls/pdf/nscl.pdf
27. Reck M. et al. Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2014; 25 (Suppl. 3): iii27–39.
28. Leighl NB et al. Molecular testing for selection of patients with lung cancer for epidermal growth factor receptor and anaplastic lymphoma kinase tyrosine kinase inhibitors: American Society of Clinical Oncology endorsement of the College of American Pathologists/International Association for the study of lung cancer/association for molecular pathology guideline. J Clin Oncol 2014; 32 (32): 3673–9.
29. Gorbunova V.A., Artamonova E.V., Breder V.V. i dr. Prakticheskie rekomendatsii po lekarstvennomu lecheniiu nemelkokletochnogo raka legkogo. Zlokachestvennye opukholi. 2016; 4. (Spetsvyp. 2): 22–33. [in Russian]
30. Johnson BE et al. A multicenter effort to identify driver mutations and employ targeted therapy in patients with lung adenocarcinomas: The Lung Cancer Mutation Consortium (LCMC). J Clin Oncol 2013; 31 (Suppl.): abstr. 8019.
31. Maemondo M et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010; 362: 2380–8.
32. Mitsudomi T et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 2010; 11: 121–8.
33. Lin JJ et al. Five-Year Survival in EGFR-Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs.  J Thorac Oncol 2016; 11 (4): 556–65.
34. Scagliotti GV et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 2008; 26: 3543–51.
35. Zhang L et al. Gefitinib versus placebo as maintenance therapy in patients with locally advanced or metastatic non-small-cell lung cancer (INFORM; C-TONG 0804): a multicentre, double-blind randomised phase 3 trial. Lancet Oncol 2012; 13 (5): 466–75.
36. Burotto M et al. Gefitinib and erlotinib in metastatic non-small cell lung cancer: a meta-analysis of toxicity and efficacy of randomized clinical trials. Oncologist 2015; 20: 400–10.
37. Park K et al. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol 2016; 17: 577–89.
38. Park K et al. First-Line Erlotinib Therapy Until and Beyond Response Evaluation Criteria in Solid Tumors Progression in Asian Patients With Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer: The ASPIRATION Study. JAMA Oncol 2016; 2 (3): 305–12.
39. Weickhardt AJ et al. Local ablative therapy of oligoprogressive disease prolongs disease control by tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer. J Thorac Oncol 2012; 7 (12): 1807–14.
40. Cortot AB, Jänne PA. Molecular mechanisms of resistance in epidermal growth factor receptor-mutant lung adenocarcinomas. Eur Respir Rev 2014; 23 (133): 356–66.
41. Jackman D et al. Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. J Clin Oncol 2010; 28 (2): 357–60.
42. Yu HA et al. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin Cancer Res 2013; 19: 2240–7.
43. Oxnard GR et al. Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: distinct natural history of patients with tumors harboring the T790M mutation. Clin Cancer Res 2011; 17 (6): 1616–22.
44. Sun JM et al. Clinical implications of T790M mutation in patients with acquired resistance to EGFR tyrosine kinase inhibitors. Lung Cancer 2013; 82: 294–8.
45. Kuiper JL et al. Incidence of T790M mutation in (sequential) rebiopsies in EGFR-mutated NSCLC-patients. Lung Cancer 2014; 85: 19–24.
46. Li W et al. T790M mutation is associated with better efficacy of treatment beyond progression with EGFR-TKI in advanced NSCLC patients. Lung Cancer 2014; 84: 295–300.
47. Kobayashi S et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 2005; 352: 786–92.
48. Cross DA et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov 2014; 4: 1046–61.
49. Yun CH et al. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci USA 2008; 105: 2070–5.
50. Kris MG et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA 2014; 311 (19): 1998–2006.
51. Fukuoka M et al. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial) [corrected]. J Clin Oncol 2003; 21 (12): 2237–46.
52. Kris MG et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA 2003; 290: 2149–58.
53. Mok T, Yang JJ, Lam KC. Treating patients with EGFR-sensitizing mutations: first line or second line--is there a difference? J Clin Oncol 2013; 31 (8): 1081–8.
54. Park K. LUX-Lung 7: is there enough data for a final conclusion? Lancet Oncol 2016; 17 (7): e268-9.
55. Sequist LV et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 2013; 31 (27): 3327–34.

Л.В.Болотина*

Московский научно-исследовательский онкологический институт им. П.А.Герцена – филиал ФГБУ «Национальный медицинский исследовательский радиологический центр» Минздрава России. 125284, Россия, Москва, 2-й Боткинский пр., д. 3
*lbolotina@yandex.ru

________________________________________________

L.V.Bolotina*

P.A.Herzen Moscow Research Institute of Oncology of National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation. 125284, Russian Federation, Moscow, 2-i Botkinskii pr., d. 3
*lbolotina@yandex.ru