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Возможность использования ингибиторов тирозинкиназы в лечении больных немелкоклеточным раком легкого с мутациями гена рецептора эпидермального фактора роста (обзор)
Возможность использования ингибиторов тирозинкиназы в лечении больных немелкоклеточным раком легкого с мутациями гена рецептора эпидермального фактора роста (обзор)
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Аннотация
За последние 5 лет накоплен огромный опыт применения эрлотиниба и гефитиниба во 2-й линии лечения НМРЛ. Эрлотиниб также показал свою эффективность в поддерживающей терапии и был зарегистрирован в США, Европе, а также в России для поддерживающего лечения больных НМРЛ без прогрессирования заболевания после 4-х курсов индукционной терапии, включающей производные платины. В настоящее время активно проводятся исследования в Азии, США и Европе по изучению эффективности ингибиторов тирозинкиназы (гефитиниб и эрлотиниб) в 1-й линии лечения НМРЛ. В частности, стали доступны результаты исследований в азиатской и европейской группах пациентов, демонстрирующие значительную эффективность эрлотиниба в 1-й линии терапии больных НМРЛ с мутациями гена EGFR. Исследования ИТК в 1-й линии терапии НМРЛ при наличии активирующих мутаций EGFR являются очень обнадеживающими. Они позволят индивидуализировать терапию больных на самых ранних этапах лечения, что может способствовать значительному увеличению продолжительности и качества жизни данных больных.
Ключевые слова: рецепторы эпидермального фактора роста (EGFR), ингибиторы тирозинкиназы рецепторов (ИТК), немелкоклеточный рак легкого (НМРЛ), мутации EGFR.
Currently there are a lot of ongoing clinical trials in Asia, USA and Europe investigating efficacy of TKIs (gefitinib and erlotinib) in the first line treatment in NSCLC. Particularly, there is the latest data of clinical trials conducted in Asian and European populations which shows the significant efficacy of erlotinib in the first line treatment in patients with EGFR Act MUT+ NSCLC.
The investigation of TKIs as a first line treatment in patients with EGFR Act MUT+ NSCLC is very encouraging and would allow physicians to personalize treatment in early stage of care that could prolong significant survival and improve patients' quality of life.
Key words: epidermal growth factor receptor (EGFR), tyrosine kinase inhibitors (TKIs), non-small cell lung cancer (NSCLC), EGFR mutation.
Ключевые слова: рецепторы эпидермального фактора роста (EGFR), ингибиторы тирозинкиназы рецепторов (ИТК), немелкоклеточный рак легкого (НМРЛ), мутации EGFR.
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Currently there are a lot of ongoing clinical trials in Asia, USA and Europe investigating efficacy of TKIs (gefitinib and erlotinib) in the first line treatment in NSCLC. Particularly, there is the latest data of clinical trials conducted in Asian and European populations which shows the significant efficacy of erlotinib in the first line treatment in patients with EGFR Act MUT+ NSCLC.
The investigation of TKIs as a first line treatment in patients with EGFR Act MUT+ NSCLC is very encouraging and would allow physicians to personalize treatment in early stage of care that could prolong significant survival and improve patients' quality of life.
Key words: epidermal growth factor receptor (EGFR), tyrosine kinase inhibitors (TKIs), non-small cell lung cancer (NSCLC), EGFR mutation.
Полный текст
Список литературы
1. Shepherd FA, Rodrigues P, Ciuleanu T et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005; 353: 123–32.
2. Thatcher N, Chang A, Parioh P et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer. Results from randomized, placebo-controlled, multi-center study (Iressa Survival evaluation in Lung Cancer). Lancet 2005; 366: 1527–37.
3. Kim ES, Hirch V, Mok T et al. Gefitined versus doxetaxel in previously treated non-small-cell lung cancer (INTEREST):a randomized phase III trial. Lancet 2008; 372: 1809–18.
4. Vamvakas L, Agelaki S, Kentepozidis NK et al. Pemetrexed (MTA) compared with erlotinib (ERL) in pretreated patients with advanced non-small cell lung cancer (NSCLC): Results of a randomized phase III Hellenic Oncology Research Group trial. Journal of Clinical Oncology, 2010 ASCO Annual Meeting Proceedings (Post-Meeting Edition). 2010; 28 (Suppl. 15), May 20 Suppl.: 7519. C2010 Am Soc Clin Oncol.
5. Ciuleanu T, Stelmakh L, Cicenas S et al. Erlotinib versus docetaxel or pemetrexed as second-line therapy in patients with advanced non-small-cell lung cancer (NSCLC) and poor prognosis: efficacy and safety results from the phase III TITAN study. IASLC Chicago 2010. LBOA5.
6. NCCN Clinical Practice Guidelines in Oncology. Non-Small Cell Lung Cancer. V1. 2011 www.nccn.org
7. ESMO Clinical Practice Guidelines. Annals of Oncology 2010; 21 (Suppl. 5).
8. Cappuzzo F, Ciuleanu T, Stelmakh L et al. Erlotinib as maintenance treatment in advanced nonsmall-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol 2010; 11: 521–9.
9. Zhou1 C, Wu2 Y-L, Chen3 G et al. Efficacy results from the randomised phase III OPTIMAL (CTONG 0802) study comparing first line erlotinib versus carboplatin (CBDCA) plus gemcitabine (GEM), in Chinese advanced non-small-cell lung cancer (NSCLC) patients (pts) with EGFR activating mutations. Abstract ASCO 2010 LBA13.
10. Mok TS, Wu YL, Thongprasert S et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947–57.
11. Paz-Ares L, Soulières D, Melezínek I et al. Clinical outcomes in non-small-cell lung cancer patients with EGFR mutations: pooled analysis. J Cell Mol Med 2010; 14 (1 2): 51–69.
12. Kim D, Lee S, Lee J et al. A multicenter phase II study to evaluate efficacy and safety of gefitinib as the first-line treatment for Korean patients (pts) with advanced pulmonary adenocarcinoma harboring EGFR mutations. J Clin Oncol 2009; 27: 423s.
13. Maemondo M, Inoue A, Kobayashi K et al. Gefitinib or Chemotherapy for Non–Small-Cell Lung Cancer with Mutated EGFR. N Engl J Med 2010; 362: 2380–8.
14. 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.
15. Rosell R, Moran T, Queralt C et al. Screening for Epidermal Growth Factor Receptor Mutations in Lung Cancer. N Engl J Med 2009; 361: 958–67.
16. Jänne PA et al. Randomized Phase II trial of erlotinib (E) alone or in combination with carboplatin/paclitaxel (CP) in never or light former smokers with advanced lung adenocarcinoma; J Clin Oncol 2010; 28: 7s (Suppl.; abstr. 7503).
17. Media release from 28/01/2011 «Early successful readout of Tarceva study in a distinct form of lung cancer» http://www.roche.com/media/media_releases.htm
18. Martin Reck et al. Erlotinib in Advanced Non-small Cell Lung Cancer Efficacy and Safety Findings of the Global Phase IV Tarceva Lung Cancer Survival Treatment Study. J Thorac Oncol 2010; 5 (10): 1616–22.
2. Thatcher N, Chang A, Parioh P et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer. Results from randomized, placebo-controlled, multi-center study (Iressa Survival evaluation in Lung Cancer). Lancet 2005; 366: 1527–37.
3. Kim ES, Hirch V, Mok T et al. Gefitined versus doxetaxel in previously treated non-small-cell lung cancer (INTEREST):a randomized phase III trial. Lancet 2008; 372: 1809–18.
4. Vamvakas L, Agelaki S, Kentepozidis NK et al. Pemetrexed (MTA) compared with erlotinib (ERL) in pretreated patients with advanced non-small cell lung cancer (NSCLC): Results of a randomized phase III Hellenic Oncology Research Group trial. Journal of Clinical Oncology, 2010 ASCO Annual Meeting Proceedings (Post-Meeting Edition). 2010; 28 (Suppl. 15), May 20 Suppl.: 7519. C2010 Am Soc Clin Oncol.
5. Ciuleanu T, Stelmakh L, Cicenas S et al. Erlotinib versus docetaxel or pemetrexed as second-line therapy in patients with advanced non-small-cell lung cancer (NSCLC) and poor prognosis: efficacy and safety results from the phase III TITAN study. IASLC Chicago 2010. LBOA5.
6. NCCN Clinical Practice Guidelines in Oncology. Non-Small Cell Lung Cancer. V1. 2011 www.nccn.org
7. ESMO Clinical Practice Guidelines. Annals of Oncology 2010; 21 (Suppl. 5).
8. Cappuzzo F, Ciuleanu T, Stelmakh L et al. Erlotinib as maintenance treatment in advanced nonsmall-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol 2010; 11: 521–9.
9. Zhou1 C, Wu2 Y-L, Chen3 G et al. Efficacy results from the randomised phase III OPTIMAL (CTONG 0802) study comparing first line erlotinib versus carboplatin (CBDCA) plus gemcitabine (GEM), in Chinese advanced non-small-cell lung cancer (NSCLC) patients (pts) with EGFR activating mutations. Abstract ASCO 2010 LBA13.
10. Mok TS, Wu YL, Thongprasert S et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947–57.
11. Paz-Ares L, Soulières D, Melezínek I et al. Clinical outcomes in non-small-cell lung cancer patients with EGFR mutations: pooled analysis. J Cell Mol Med 2010; 14 (1 2): 51–69.
12. Kim D, Lee S, Lee J et al. A multicenter phase II study to evaluate efficacy and safety of gefitinib as the first-line treatment for Korean patients (pts) with advanced pulmonary adenocarcinoma harboring EGFR mutations. J Clin Oncol 2009; 27: 423s.
13. Maemondo M, Inoue A, Kobayashi K et al. Gefitinib or Chemotherapy for Non–Small-Cell Lung Cancer with Mutated EGFR. N Engl J Med 2010; 362: 2380–8.
14. 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.
15. Rosell R, Moran T, Queralt C et al. Screening for Epidermal Growth Factor Receptor Mutations in Lung Cancer. N Engl J Med 2009; 361: 958–67.
16. Jänne PA et al. Randomized Phase II trial of erlotinib (E) alone or in combination with carboplatin/paclitaxel (CP) in never or light former smokers with advanced lung adenocarcinoma; J Clin Oncol 2010; 28: 7s (Suppl.; abstr. 7503).
17. Media release from 28/01/2011 «Early successful readout of Tarceva study in a distinct form of lung cancer» http://www.roche.com/media/media_releases.htm
18. Martin Reck et al. Erlotinib in Advanced Non-small Cell Lung Cancer Efficacy and Safety Findings of the Global Phase IV Tarceva Lung Cancer Survival Treatment Study. J Thorac Oncol 2010; 5 (10): 1616–22.
Авторы
Н.Ф.Орел
Онкологический научный центр им. Н.Н.Блохина РАМН, Москва
Oncology Scientific Center of RAMS named after N.N. Blokhin, Moscow
Онкологический научный центр им. Н.Н.Блохина РАМН, Москва
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Oncology Scientific Center of RAMS named after N.N. Blokhin, Moscow
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