Осимертиниб в 1-й линии терапии EGFR-позитивного немелкоклеточного рака легкого

Реутова Е.В., Лактионов К.П., Юдин Д.И. и др. Осимертиниб в 1-й линии терапии EGFR-позитивного немелкоклеточного рака легкого. Современная Онкология. 2019; 21 (3): 17–20. DOI: 10.26442/18151434.2019.3.190659

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Reutova E.V., Laktionov K.P., Iudin D.I. et al. Osimertinib for the first-line treatment of EGFR-positive non-small cell lung cancer. Journal of Modern Oncology. 2019; 21 (3): 17–20. DOI: 10.26442/18151434.2019.3.190659

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Аннотация

За последнее столетие рак легкого стал одним из наиболее распространенных злокачественных новообразований. Прогноз у пациентов с метастатическим и местно-распространенным немелкоклеточным раком легкого (НМРЛ) был крайне пессимистичным. Общая выживаемость на фоне стандартной платиносодержащей комбинированной химиотерапии не превышала 10 мес. Подход к выбору лечебной тактики, а именно конкретного химиотерапевтического режима, был эмпирическим. Коренным образом ситуация изменилась с изучением молекулярно-генетических нарушений, которые способствуют развитию опухоли, и появлением таргетной терапии. До настоящего времени основным подходом в лечении больных НМРЛ с активирующими мутациями было последовательное применение ингибиторов тирозинкиназ (ИТК) I поколения, далее в случае прогрессирования – назначение препаратов последующих поколений либо химиотерапия. Однако в последнее время эта тенденция меняется, таргетные препараты новых поколений имеют достоверное преимущество по времени до прогрессирования, лучшему интракраниальному контролю, более благоприятному профилю безопасности, что закрепляет за ними место в 1-й линии терапии. Последние данные подтверждают и улучшение общей выживаемости. В данной статье рассматривается ситуация на примере лечения больных НМРЛ с наличием мутации в гене EGFR.

Ключевые слова: ингибиторы тирозинкиназы EGFR, рак легкого, немелкоклеточный рак легкого, осимертиниб.

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In the past century, lung cancer has become one of the most prevalent malignant neoplasms. The prognosis for patients with metastatic and locally advanced non-small cell lung cancer (NSCLC) was extremely pessimistic. The overall survival on standard platinum-based chemotherapy did not exceed 10 months. The treatment tactics choice, namely choice of specific chemotherapeutic regimen, was empirical. The situation has changed dramatically with the study of molecular-genetic disorders that contribute to a tumor development and targeted therapy availability. Until recently, the main approach to the treatment of patients with NSCLC with activating mutations was the use of first-generation tyrosine kinase inhibitors (TKI), then, in the case of disease progression, the administration of next generations drugs or chemotherapy. However, this trend has been changing lately, new generation of targeted drugs have a significant advantage in time till progression, better intracranial control, a more favorable safety profile, that establish them as first-line treatment. Recent data confirms also an improvement of overall survival. This article discusses the situation in EGFR-postive NSCLC.

Key words: EGFR tyrosine kinase inhibitors, lung cancer, non-small cell lung cancer, osimertinib.

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Список литературы

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2. Lynch TJ et al. Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non-Small-Cell Lung Cancer to Gefitinib. NEJM 2004; 350: 2129–39.
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7. 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.
8. Yoshioka H et al. Final overall survival results of WJTOG 3405, a randomized phase 3 trial comparing gefitinib (G) with cisplatin plus docetaxel (CD) as the first-line treatment for patients with non-small cell lung cancer (NSCLC) harboring mutations of the epidermal growt. J Clin Oncol 2014; 32: 8117.
9. Mok TS et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947–57.
10. 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.
11. Zhou C 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 multicentre, open-label, randomised, phase 3 study. Lancet Oncol 2011; 12: 735–42.
12. Zhou C et al. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL. CTONG-0802). Ann Oncol 2015; 26: 1877–83.
13. 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: 3327–34.
14. Wu Y-L et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol 2014; 15: 213–22.
15. Yang JC, Wu YL, Schuler M et al. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUXLung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol 2015; 16: 141–51. DOI: 10.1016/S1470-2045(14)71173-8
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19. Seto T, Kato T, Nishio M et al. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, Phase II study. Lancet Oncol 2014; 15: 1236–44.
20. Saito H, Fukuhara T, Furuya N et al. Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, Phase III trial. Lancet Oncol 2019; 20: 625–35.
21. Инструкция по применению лекарственного препарата для медицинского применения осимертиниб от 11.05.2018. Регистрационное удостоверение ЛП-004492 от 18.10.2017.
[Instruktsiia po primeneniiu lekarstvennogo preparata dlia meditsinskogo primeneniia osimertinib ot 11.05.2018. Registratsionnoe udostoverenie LP-004492 ot 18.10.2017 (in Russian).]
22. Janne PA et al. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med 2015; 372: 1689–99.
23. Colclough N et al. Preclinical comparison of the blood brain barrier (BBB) permeability of osimertinib (AZD9291) with other irreversible next generation EGFR TKIs. EJC December 2016; 69 (Suppl. 1): S28.
24. Soria JC, Ohe Y, Vansteenkiste J et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med 2018; 378 (2): 113–25. DOI: 10.1056/NEJMoa1713137
25. Ramalingam et al. Osimertinib vs comparator EGFR-TKI as first-line treatment for EGFRm advanced NSCLC (FLAURA): Final overall survival analysis. Ann Oncol 2019; 30 (Suppl. 5): v851–v934.
26. Портал Национального института рака США clinicaltrials.gov// Эл. ресурс: https://clinicaltrials.gov/ct2/ results?cond=&term=osimertinib&cntry=&state=&city=&dist=
[Portal Natsional'nogo instituta raka SShA clinicaltrials.gov// El. resurs: https://clinicaltrials.gov/ct2/results?cond=&term=osimertinib&cntry=&state=&...= (in Russian).]

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1. Sharma SV et al. Epidermal growth factor receptor mutations in lung cancer. Nature Rev Cancer 2007; 7: 169–81.
2. Lynch TJ et al. Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non-Small-Cell Lung Cancer to Gefitinib. NEJM 2004; 350: 2129–39.
3. Pao W et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004; 304: 1497–500.
4. Cheng et al. Molecular pathology of lung cancer: key to personalized medicine.Modern Pathology 2012; 25: 347–69.
5. 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 CMRO 2015; 31 (6): 1117–27.
6. Novello S et al. Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2016; 27: v1–v27.
7. 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.
8. Yoshioka H et al. Final overall survival results of WJTOG 3405, a randomized phase 3 trial comparing gefitinib (G) with cisplatin plus docetaxel (CD) as the first-line treatment for patients with non-small cell lung cancer (NSCLC) harboring mutations of the epidermal growt. J Clin Oncol 2014; 32: 8117.
9. Mok TS et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947–57.
10. 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.
11. Zhou C 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 multicentre, open-label, randomised, phase 3 study. Lancet Oncol 2011; 12: 735–42.
12. Zhou C et al. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL. CTONG-0802). Ann Oncol 2015; 26: 1877–83.
13. 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: 3327–34.
14. Wu Y-L et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol 2014; 15: 213–22.
15. Yang JC, Wu YL, Schuler M et al. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUXLung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol 2015; 16: 141–51. DOI: 10.1016/S1470-2045(14)71173-8
16. Urata et al. Randomized Phase III Study Comparing Gefitinib With Erlotinib in Patients With Previously Treated Advanced Lung Adenocarcinoma: WJOG 5108L. J Clin Oncol 2016; 34 (27): 3248–57.
17. Paz-Ares L et al. Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: overall survival data from the phase IIb LUX-Lung 7 trial. Ann Oncol 2017; 28 (2): 270–7.
18. Soria JC, Wu YL, Nakagawa K et al. Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation-positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial. Lancet Oncol 2015; 16: 990–8.
19. Seto T, Kato T, Nishio M et al. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, Phase II study. Lancet Oncol 2014; 15: 1236–44.
20. Saito H, Fukuhara T, Furuya N et al. Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, Phase III trial. Lancet Oncol 2019; 20: 625–35.
21. Instruktsiia po primeneniiu lekarstvennogo preparata dlia meditsinskogo primeneniia osimertinib ot 11.05.2018. Registratsionnoe udostoverenie LP-004492 ot 18.10.2017 (in Russian).
22. Janne PA et al. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med 2015; 372: 1689–99.
23. Colclough N et al. Preclinical comparison of the blood brain barrier (BBB) permeability of osimertinib (AZD9291) with other irreversible next generation EGFR TKIs. EJC December 2016; 69 (Suppl. 1): S28.
24. Soria JC, Ohe Y, Vansteenkiste J et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med 2018; 378 (2): 113–25. DOI: 10.1056/NEJMoa1713137
25. Ramalingam et al. Osimertinib vs comparator EGFR-TKI as first-line treatment for EGFRm advanced NSCLC (FLAURA): Final overall survival analysis. Ann Oncol 2019; 30 (Suppl. 5): v851–v934.
26. Portal Natsional'nogo instituta raka SShA clinicaltrials.gov// El. resurs: https://clinicaltrials.gov/ct2/results?cond=&term=osimertinib&cntry=&state=&...= (in Russian).

Авторы

Е.В. Реутова*1, К.П. Лактионов1, Д.И. Юдин1, Л.А. Нелюбина1, Г.К. Горохова2, А.В. Егорова2

1 ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России, Москва, Россия;
2 ФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия
*evreutova@rambler.ru

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Elena V. Reutova*1, Konstantin P. Laktionov1, Denis I. Iudin1, Lidiia A. Neliubina1, Galina K. Gorokhova2, Angelina V. Egorova2

1 Blokhin National Medical Research Center of Oncology, Moscow, Russia;
2 Pirogov Russian National Research Medical University, Moscow, Russia
*evreutova@rambler.ru

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