Preview

Медицинский Совет

Расширенный поиск

Афатиниб: новые возможности терапии рака легкого с наличием активирующих мутаций EGFR

https://doi.org/10.21518/2079-701X-2015-8-50-54

Аннотация

Применение ингибиторов EGFR первого поколения существенно улучшило результаты лекарственного лечения пациентов с метастатическим немелкоклеточным раком легкого, включая значимое увеличение частоты достижения объективного эффекта и времени до прогрессирования болезни. В настоящее время арсенал эффективных препаратов расширился за счет внедрения в клиническую практику ингибитора EGFR второго поколения - афатиниба. По данным клинических исследований, максимальная реализация его лечебного эффекта зависит не только от статуса активирующей мутации, но и от ее типа. При наличии мутации EGFr в 19 экзоне афатиниб значимо увеличивает и медиану общей выживаемости. Это представляется чрезвычайно важным обстоятельством, определяющим выбор рационального лечения. Афатиниб эффективен также при развитии резистентности к ингибиторам EGFR первого поколения и представляет собой альтернативный вариант второй линии терапии. Трудно переоценить данное преимущество препарата, позволяющее существенно отсрочить назначение химиотерапии таким больным.

Об авторах

М. В. Степанченко
Российский онкологический научный центр им. Н.Н. Блохина, Москва
Россия


В. Г. Зайцев
Российский онкологический научный центр им. Н.Н. Блохина, Москва
Россия


С. Л. Гуторов
Российский онкологический научный центр им. Н.Н. Блохина, Москва
Россия


Список литературы

1. Suda K, Mizuuchi H, Maehara Y, et al. Acquired resistance mechanisms to tyrosine kinase inhibitors in lung cancer with activating epidermal growth factor receptor mutation -diversity, ductility, and destiny. Cancer Metastasis Rev., 2012, 31: 807-814.

2. Masahiro F, Yi-Long W, Sumitra T, 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 29:28662874.

3. Sun JM, Lee KH, Kim SW, et al. Gefitinib versus pemetrexed as second-line treatment in patients with nonsmall cell lung cancer previously treated with platinum-based chemotherapy (KCSG-LU08-01) [published online ahead of print June 6, 2012]. Cancer. 2012. doi:10.1002/cncr.27630.

4. Zhang L, Ma S, Song X, 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., 2011, 13(5): 466-475.

5. Wu Y-L, Zhou C et al. First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study. Ann Oncol (2015) doi: 10.1093/annonc/mdv270 First published online: June 23, 2015.

6. Rosell R, Carcereny E, Moran T, et al.Erlotinib versus standard chemotherapy as fi rst-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial Rafael Rosell, Enric Carcereny, RadjGervais, Alain Vergnenegre, Bartomeu Massuti, Lancet Oncol, 2012, 13: 239-46.

7. Lee C, Brown C, Gralla R, etal. Impact of EGFR inhibitor in non-small cell lung cancer on progression-free and overall survival: a meta-analysis. J Natl Cancer Inst, 2013, 105: 595-605.

8. Reck М, Popat S, Reinmuth N, 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-iii39.

9. Socinski M, Evans T, Gettinger S, et al. Treatment of stage IV non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest (2013) 143: 341S-68S.10.1378.

10. Hynes N, Lane H. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer, 2005, 5: 341-354.

11. Li D, Ambrogio L, Shimamura T, et al. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene, 2008, 27: 4702-4711.

12. Sequist V, Yang J, Yamamoto N, et al: Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcino-ma with EGFR mutations. J Clin Oncol, 2013, 31: 3327- 3334.

13. Yi-Long W, Caicun Z, Cheng-Ping H, et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer har-bouringEGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol, 2014, 15: 213-2.

14. Yang J, Sequist L, Schuler M, et al. Overall survival in patients with advanced non-small-cell lung cancer harbouring common (del19/L858R) EGFR mutations: pooled analysis of two large open-label phase III studies (LUX-lung 3 and LUX-lung 6) comparing afatinib with chemotherapy. J Clin Oncol, 2014, 32(5s): abstr8004.

15. Yang J, Wu YL, Schuler M, et al. Afatinib versus cisplatin-based chemotherapy forEGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol, 2015, 16:141-15.

16. Yu HA, Arcila ME, Hellmann MD et al. Poor response to erlotinib in patients with tumors containing baseline EGFR T790M mutations found by routine clinical molecular testing. Ann. Oncol., 2014, 25(2), 423-428.

17. Hirsh V, Managing treatment-related adverse events associated with EGFRtyrosine kinase inhibitors in advanced non-small-cell lung cancer Curr Oncol. 2011 Jun; 18(3): 126-138.

18. Mok T, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocar-cinoma. N Engl J Med, 2009, 361: 947-57.10.1056/NEJMoa0810699.

19. Zhou C, Wu YL, Chen G, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multi-centre, open label, randomized, phase 3 study. Lancet Oncol, 2011, 12:735-42.10.1016/S1470-2045(11)70184-X.

20. Sequist L, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus peme-trexed in patients with metastatic lung ade-nocarcinoma with EGFR mutations. J Clin Oncol, 2013, 31:3327-3410.1200/ JCO.2012.44.2806.

21. Alfredo T, Rosa L, Chiara L, et al. Aieta Which tyrosine kinase inhibitor should be recommended as initialtreatment for non-small cell lung cancer patients with EGFR mutations? Med Oncol, 2014, 31:78 DOI 10.1007/s12032-014-0078-5.

22. Liang W, Wu X, Fang W. Network meta-analysis oferlotinib, gefitinib, afatinib and icotinibin patients with advanced non small cell lung cancer harboring EGFR mutations. PLoS ONE, 2014, 9(2): 85245.

23. Joshi M, Rizvi S, Belani C. Afatinib for the treatment of metastatic non-small cell lung cancer. Cancer Manag Res., 2015, 19,7: 75-82.

24. Vincent A, Vera H, Jacques C, et al. Afatinib versus placebo for patients with advanced, meta-static non-small-cell lung cancer after failure oferlotinib, gefitinib, or both, and one ortwo lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial Vincent. Lancet Oncol, 2012, 13: 528-38.

25. Schuler M, Yang CH, Park K, et al. Continuation of afatinib beyond progression: Results of a randomized, open-label, phase III trial of afatinib plus paclitaxel versus investigator's choice chemotherapy in patients with meta-static non-small cell lung cancer progressed on erlotinib/gefitinib (E/G) and afatinib - LUX-Lung 5. J Clin Oncol, 2014 32: 5.

26. Sebastian M, Schmittel A and Reck V. First-line treatment of EGFR-mutated non-small cell lung cancer: critical review on study methodology. Eur Respir Rev, 2014, 23: 92-105.

27. Passaro A, Di Maio M, et al. Management of Nonhematologic Toxicities Associated With Different EGFR-TKIs in Advanced NSCLC: A Comparison Analysis. Clinical Lung Cancer, 2014, 15(4), 307-12, Elsevier Inc.


Рецензия

Для цитирования:


Степанченко МВ, Зайцев ВГ, Гуторов СЛ. Афатиниб: новые возможности терапии рака легкого с наличием активирующих мутаций EGFR. Медицинский Совет. 2015;(8):50-54. https://doi.org/10.21518/2079-701X-2015-8-50-54

For citation:


Stepanchenko MV, Zaitsev VG, Gutorov SL. Afatinib: new treatment options for lung cancer with activating EGFR mutations. Meditsinskiy sovet = Medical Council. 2015;(8):50-54. (In Russ.) https://doi.org/10.21518/2079-701X-2015-8-50-54

Просмотров: 420


Creative Commons License
Контент доступен под лицензией Creative Commons Attribution 4.0 License.


ISSN 2079-701X (Print)
ISSN 2658-5790 (Online)