Представлены данные о современном состоянии проблемы лекарственного лечения немелкоклеточного рака легкого. Показано прогностическое значение ряда мутаций в опухоли и их роль в качестве мишеней для таргетной терапии. Дан краткий анализ подходов к выбору рациональных режимов терапии в зависимости от морфологического строения опухоли.
The data on the current status for drug treatment of non-small cell lung cancer are presented. The prognostic significance of several mutations in tumors and their role as a target for anticancer therapy are shown. A brief analysis of the approaches for rational treatment regimens based on histology subtypes of non-small cell lung cancer is performed.
1. Johnson ML, Sima C, Paik PK et al. Association of KRAS and EGFR mutations with survival in patients with advanced lung adenocarcinoma. J Clin Oncol 2010; 28. Abstr. 7541.
2. Movsas B, Brahmer J, Paller C et al. Non-Small-Cell Lung Cancer. 13th ed. Cancer Management 2011. Downloaded from Cancernetwork.com
3. Ardizzoni A, Boni L, Tiseo M et al. Cisplatin Versus Carboplatin-Based Chemotherapy in First-Line Treatment of Advanced Non-Small-Cell Lung Cancer: An Individual Patient Data Meta-analysis. J Natl Cancer Inst 2007; 99: 847–57.
4. Scagliotti G, Parikh P, Pawel J 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.
5. Rossi A, Ricciardi S, Maione P et al. Pemetrexed in the treatment of advanced non-squamous lung cancer. Lung Cancer 2009; 66: 141–9.
6. Socinski MA, Bondarenko IN, Karaseva NA et al. Results of a randomized, phase III trial of nab-paclitaxel (nab-P) and carboplatin (C) compared with cremophor-based paclitaxel (P) and carboplatin as first-line therapy in advanced non-small cell lung cancer (NSCLC). ASCO Meeting Abstracts 2010; 28: LBA7511.
7. Sandler A, Gray R, Perry MC et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006; 355: 2542–50.
8. Ciuleanu T, Brodowicz T, Zielinski C 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.
9. Langer CJ, Besse B, Gualberto A et al. The Evolving Role of Histology in the Management of Advanced Non-Small-Cell Lung Cancer. J Clin Oncol 2010; 20: 5311–20.
10. Travis WD, Brambilla E, Noguchi M et al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 2011; 5: 244–85.
11. Kim SE, Hirch V, Mok T et al. Gefitinib versus docetaxel in previously treated patients with non-small-cell-lung-cancer (INTEREST): a randomized phase III trial. Lancet 2008; 372: 1809–18.
12. Cappuzzo F, Coudert B, Wierzbicki R et al. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised placebo-controlled phase III study. Lancet Oncol 2010; 11: 521–9.
13. Hirsch FR, Varella-Garcia M, Bunn PA et al. Molecolar predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non-small-cell lung cancer. J Clin Oncol 2006; 24: 5034–42.
14. Florescu M, Hasan B, Seymour L et al. A clinical prognostic index for patients treated with erlotinib in National Cancer Institute of Canada Clinical Trials Group study BR.21. J Thorac Oncol 2008; 3 (6): 590–8.
15. Рекомендации по отбору пациентов для эффективного лечения эрлотинибом местно-распространенного и метастатического немелкоклеточного рака легкого. Практические рекомендации для врачей. Под ред. И.В.Поддубной. М., 2010.
16. Mok TS, Wu YL, Thongprasert S et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947–57.
17. Sequist LV, Martins RG, Spigel D et al. First-Line Gefitinib in Patients With Advanced Non-Small-Cell Lung Cancer Harboring Somatic EGFR Mutations. J Clin Oncol 2008; 26: 2442–9.
18. Mitsudomi T, Morita S, Yatabe Y 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.
19. Maemondo M, Inoue A, Kobayashi K et al. Gefitinib or chemotherapy for non small cell lung cancer with mutated tumour. N Engl J Med 2010; 362: 2380–8.
20. Zhou C, Wu Y, Chen G et al. Preliminary results of randomized phase III study comparing efficacy and safety of first-line erlotinib versus carboplatin (CBDCA) plus gemcitabine (GEM) in Chinese advanced non-small cell lung cancer (NSCLC) patients (pts) with EGFR-activating mutations (OPTIMAL). ASCO Meeting Abstracts 2010; 28: p. 7575.
21. Rosell R, Gervais R, Vergnenegre A et al. Erlotinib versus chemotherapy (CT) in advanced non-small cell lung cancer (NSCLC) patients (p) with epidermal growth factor receptor (EGFR) mutations: Interim results of the European Erlotinib Versus Chemotherapy (EURTAC) phase III randomized trial. ASCO Meeting Abstracts 2011; 29: p. 7503.
22. Minegishi Y, Maemondo M, Okinaga S et al. First-line gefitinib therapy for elder advancednon-small cell lung cancer patients with epidermal growth factor receptor mutations: multicenter phase II trial (NEJ 003 study). J Clin Oncol 2010; 28. Abstr. 7561.
23. Roberts PJ, Stinchcombe TE, Der CJ et al. Personalized Medicine in Non-Small-Cell Lung Cancer: Is KRAS a Useful Marker in Selecting Patients for Epidermal Growth Factor Receptor-Targeted Therapy. J Clin Oncol 2010; 28: 4769–77.
24. Mao C, Qiu LX, Liao RY et al. KRAS mutations and resistance to EGFR-TKIs treatment in patients with non-small cell lung cancer: A meta-analysis of 22 studies. Lung Cancer 2010; 69: 272–8.
25. Linardou H, Dahabreh IJ, Kanaloupiti D et al. Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: A systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer. Lancet Oncol 2008; 9: 962–72.
26. Cappuzzo F, Coudert BP, Wierzbicki R et al. Efficacy and safety of erlotinib as first-line maintenance in NSCLC following non-progression with chemotherapy: Results from the phase III SATURN study. 13th World Conference on Lung Cancer, San Francisco, CA 2009; 4. Abstr. A2.1.
27. Kim ES, Hirsh V, Mok T et al. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): A randomised phase III trial. Lancet 2008; 372: 1809–18.
28. Pirker R, Pereira JR, Szczesna A et al: Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): An open-label randomised phase III trial. Lancet 2009; 373: 1525–31.
29. Lynch TJ, Patel T, Dreisbach L et al. Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: Results of the randomized multicenter phase III trial BMS099. J Clin Oncol 2010; 28: 911–7.
30. Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol 2011; 12: 175–80.
31. Cappuzzo F, Bemis L, Varella-Garcia M. HER-2 mutation and response to trastuzumab therapy in non-small-cell lung cancer. N Engl J Med 2006; 354: 2619–21.
32. De Greve J, Teugels E, De Mey J et al. Clinical activity of BIBW2992, an irreversible inhibitor of EGFR and HER-2 in adenocarcinoma of the lung with mutations in the kinase domain of HER-2-neu. J Thorac Oncol 2009; 4: s. 307.
33. Hanna NH, Pawel J, Reck M et al. Carboplatin/paclitaxel with/without sorafenib in chemonaive patients with stage IIIb-IV non-small cell lung cancer: interim analysis (ia) results from a randomized phase III trial (ESCAPE). J Thorac Oncol 2008; 3 (Suppl. 7): s268. Abstr. 214.
34. Bean J, Brennan C, Shih JY et al. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. PNAS 2007; 104 (52): 20932–7. http://www.pnas.org
35. Engelman JA, Zejnullahu K, Mitsudomi T et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 2007; 316: 1039–43. Proc Natl Acad Sci USA 2007; 104: 20932–7.
Авторы
Е.И.Борисова, С.Л.Гуторов
Российский онкологический научный центр им. Н.Н.Блохина РАМН, Москва