Адъювантная таргетная терапия при немелкоклеточном раке легкого

Лактионов К.К., Казаков А.М., Гордиев М.Г. и др. Адъювантная таргетная терапия при немелкоклеточном раке легкого. Современная Онкология. 2020; 22 (2): 104–107. DOI: 10.26442/18151434.2020.2.200200

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Laktionov K.K., Kazakov A.M., Gordiev M.G. et al. Adjuvant targeted therapy for non-small cell lung cancer. Journal of Modern Oncology. 2020; 22 (2): 104–107. DOI: 10.26442/18151434.2020.2.200200

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Аннотация

Немелкоклеточный рак легкого (НМРЛ) является гетерогенной группой заболеваний с широким спектром возможных таргетных активирующих мутаций. В связи с этим на данный момент большое внимание уделяется такой опции лечения пациентов с НМРЛ, как адъювантная таргетная терапия после проведенного радикального хирургического лечения. Активный интерес к этой опции связан с несколькими причинами: достаточной низкой эффективностью адъювантной химиотерапии, возросшими возможностями молекулярно-генетических методов определения активирующих мутаций, широким введением в клиническую практику жидкостной биопсии, а также результатами, которые демонстрируют исследования, посвященные применению таргетной терапии как в лечении распространенных форм НМРЛ, так и в адъювантном режиме. Результаты таких исследований, как SELECT, ADJUVANT/CTONG1104, ADAURA, показали преимущество применения адъювантной таргетной терапии по сравнению с химиотерапией, плацебо или историческим контролем. Возможность определения циркулирующей опухолевой ДНК как маркера минимальной резидуальной болезни после оперативного лечения, а также определение мутационного профиля при помощи минимально инвазивного метода – жидкостной биопсии позволит еще более персонализированно подходить к назначению адъювантной терапии. Все это делает применение адъювантной таргетной терапии перспективной и эффективной опцией лечения.

Ключевые слова: немелкоклеточный рак легкого, адъювантная терапия, таргетная терапия, циркулирующая опухолевая ДНК.

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Non-small cell lung cancer (NSCLC) is a heterogeneous group of diseases with a wide range of possible targeted activating mutations. In this regard, a lot of attention is paid to such treatment of patients with NSCLC as adjuvant targeted therapy after radical surgical treatment, nowadays. The active interest in this option is associated with several reasons: sufficient low efficacy of adjuvant chemotherapy, increased capabilities of molecular genetic methods to determine the activating mutations, extensive introduction of liquid biopsy into the clinical practice, as well as the results of the trials associated with the use of targeted therapy both in the treatment of advanced forms of NSCLC and in an adjuvant regimen. The results of such trials as SELECT, ADJUVANT/CTONG1104, ADAURA have shown the benefit of adjuvant targeted therapy in comparison with chemotherapy, placebo or historical control. The ability to identify circulating tumor DNA as a marker of minimal residual disease after surgical treatment, as well as the determination of the mutation profile using the minimally invasive method such as the fluid biopsy will allow achieving an even more personalized approach to the appointment of adjuvant therapy. All this makes the use of adjuvant targeted therapy a promising and effective treatment option.

Key words: non-small cell lung cancer, adjuvant therapy, targeted therapy, circulating tumor DNA.

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Список литературы

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[Laktionov K.K., Kazakov A.M., Sarantseva K.A. et al. Rol' zhidkostnoi biopsii v vybore taktiki lecheniia nemelkokletochnogo raka legkogo. Prakticheskaia onkologiia. 2020; 21 (1). DOI: 10.31917/2101046 (in Russian).]
18. Chae YK, Oh MS. Detection of Minimal Residual Disease Using ctDNA in Lung Cancer: Current Evidence and Future Directions. J Thorac Oncol 2019; 14 (1): 16–24. DOI: 10.1016/j.jtho.2018.09.022
19. Tie J, Wang Y, Tomasetti C et al. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med 2016; 8 (346): 346ra92. DOI: 10.1126/scitranslmed.aaf6219
20. Chen K, Zhao H, Shi Y et al. Perioperative Dynamic Changes in Circulating Tumor DNA in Patients with Lung Cancer (DYNAMIC). Clin Cancer Res 2019; 25 (23): 7058–67. DOI: 10.1158/1078-0432.CCR-19-1213
21. Ting Ye, Haiquan Chen. Adjuvant targeted therapy for resected NSCLC: to be or not to be? J Thorac Dis 2018; 10 (Suppl. 26): S3297–S3299. DOI: 10.21037/jtd.2018.07.111
22. Sorensen BS, Wu L, Wei W et al. Monitoring of epidermal growth factor receptor tyrosine kinase inhibitor-sensitizing and resistance mutations in the plasma DNA of patients with advanced non-small cell lung cancer during treatment with erlotinib. Cancer 2014; 120 (24): 3896–901. DOI: 10.1002/cncr.28964
23. Provencio M, Torrente M, Calvo V et al. Prognostic value of quantitative ctDNA levels in non small cell lung cancer patients. Oncotarget 2017; 9 (1): 488–94. DOI: 10.18632/oncotarget.22470

________________________________________________

1. Le Chevalier T. Adjuvant chemotherapy for resectable non-small cell lung cancer: where is it going? Ann Oncol 2010; 21 (Suppl. 7): vii196–vii198. DOI: 10.1093/annonc/mdq376
2. Arriagada R, Bergman B, Dunant A et al; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 2004; 350 (4): 351–60. DOI: 10.1056/NEJMoa031644
3. Douillard J-Y, Tribodet H, Aubert D et al. Adjuvant Cisplatin and Vinorelbine for Completely Resected Non-small Cell Lung Cancer: Subgroup Analysis of the Lung Adjuvant Cisplatin Evaluation. J Thorac Oncol 2010; 5 (2): 220–8. DOI: 10.1097/JTO.0b013e3181c814e7
4. Pennell NA, Neal JW, Chaft JE et al. SELECT: A Phase II Trial of Adjuvant Erlotinib in Patients With Resected Epidermal Growth Factor Receptor-Mutant Non-Small-Cell Lung Cancer. J Clin Oncol 2019; 37 (2): 97–104. DOI: 10.1200/JCO.18.00131
5. 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 multicentre, open-label, randomised, phase 3 study. Lancet Oncol 2011; 12 (8): 735–42.
6. Kelly K, Altorki NK, Eberhardt WE et al. Adjuvant Erlotinib Versus Placebo in Patients With Stage IB-IIIA Non-Small-Cell Lung Cancer (RADIANT): A Randomized, Double-Blind, Phase III Trial. J Clin Oncol 2015; 33 (34): 4007–14. DOI: 10.1200/JCO.2015.61.8918
7. Bethune G, Bethune D, Ridgway N, Xu Z. Epidermal growth factor receptor (EGFR) in lung cancer: an overview and update. J Thorac Dis 2010; 2 (1): 48–51. PMCID: PMC3256436.
8. Jurišić V, Obradovic J, Pavlović S, Djordjevic N. Epidermal Growth Factor Receptor Gene in Non-Small-Cell Lung Cancer: The Importance of Promoter Polymorphism Investigation. Anal Cell Pathol (Amst) 2018; 2018: 6192187. DOI: 10.1155/2018/6192187
9. Zhong WZ, Wang Q, Mao WM et al; ADJUVANT investigators. Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II–IIIA (N1–N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study. Lancet Oncol 2018; 19 (1): 139–48. DOI: 10.1016/S1470-2045 (17)30729-5
10. Shen P, Zhong W. Adjuvant EGFR TKI therapy for resectable non-small cell lung cancer: new era for personalized medicine. J Thorac Dis 2018; 10 (3): 1364–9. DOI: 10.21037/jtd.2018.03.97
11. Govindan R, Mandrekar SJ, Gerber DE et al. ALCHEMIST Trials: A Golden Opportunity to Transform Outcomes in Early Stage Non–Small Cell Lung Cancer. Clin Cancer Res 2015; 21 (24): 5439–44. DOI: 10.1158/1078-0432.CCR-15-0354
12. Ramalingam SS, Vansteenkiste J, Planchard D et al., for the FLAURA Investigators. Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC. N Engl J Med 2020; 382: 41–50. DOI: 10.1056/NEJMoa1913662
13. Mok TS, Wu Y-L, Ahn M-Ju et al., for the AURA3 Investigators. Osimertinib or Platinum–Pemetrexed in EGFR T790M–Positive Lung Cancer. N Engl J Med 2017; 376: 629–40. DOI: 10.1056/NEJMoa1612674
14. Wu YL, Herbst RS, Mann H et al. ADAURA: Phase III, Double-blind, Randomized Study of Osimertinib Versus Placebo in EGFR Mutation-positive Early-stage NSCLC After Complete Surgical Resection. Clin Lung Cancer 2018; 19 (4): e533–e536. DOI: 10.1016/j.cllc.2018.04.004
15. Herbst RS, Tsuboi M, John T. Osimertinib as adjuvant therapy in patients (pts) with stage IB–IIIA EGFR mutation positive (EGFRm) NSCLC after complete tumor resection: ADAURA. J Clin Oncol 2020; 38.
16. Hosch SB, Scheunemann P, Izbicki JR. Minimal residual disease in non-small-cell lung cancer. Semin Surg Oncol 2001; 20 (4): 278–81. DOI: 10.1002/ssu.1045
17. Laktionov K.K., Kazakov A.M., Sarantseva K.A. et al. Rol' zhidkostnoi biopsii v vybore taktiki lecheniia nemelkokletochnogo raka legkogo. Prakticheskaia onkologiia. 2020; 21 (1). DOI: 10.31917/2101046 (in Russian).
18. Chae YK, Oh MS. Detection of Minimal Residual Disease Using ctDNA in Lung Cancer: Current Evidence and Future Directions. J Thorac Oncol 2019; 14 (1): 16–24. DOI: 10.1016/j.jtho.2018.09.022
19. Tie J, Wang Y, Tomasetti C et al. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med 2016; 8 (346): 346ra92. DOI: 10.1126/scitranslmed.aaf6219
20. Chen K, Zhao H, Shi Y et al. Perioperative Dynamic Changes in Circulating Tumor DNA in Patients with Lung Cancer (DYNAMIC). Clin Cancer Res 2019; 25 (23): 7058–67. DOI: 10.1158/1078-0432.CCR-19-1213
21. Ting Ye, Haiquan Chen. Adjuvant targeted therapy for resected NSCLC: to be or not to be? J Thorac Dis 2018; 10 (Suppl. 26): S3297–S3299. DOI: 10.21037/jtd.2018.07.111
22. Sorensen BS, Wu L, Wei W et al. Monitoring of epidermal growth factor receptor tyrosine kinase inhibitor-sensitizing and resistance mutations in the plasma DNA of patients with advanced non-small cell lung cancer during treatment with erlotinib. Cancer 2014; 120 (24): 3896–901. DOI: 10.1002/cncr.28964
23. Provencio M, Torrente M, Calvo V et al. Prognostic value of quantitative ctDNA levels in non small cell lung cancer patients. Oncotarget 2017; 9 (1): 488–94. DOI: 10.18632/oncotarget.22470

Авторы

К.К. Лактионов*1,2, А.М. Казаков1, М.Г. Гордиев3, П.В. Кононец1, Б.Б. Ахмедов1, Ю.Н. Маевская1,4

1 ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России, Москва, Россия;
2 ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия;
3 ООО «Национальный БиоСервис», Санкт-Петербург, Россия;
4 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия
*lkoskos@mail.ru

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Konstantin K. Laktionov*1,2, Aleksei M. Kazakov1, Marat G. Gordiev3, Pavel V. Kononets1, Bakhrom B. Akhmedov1, Julia N. Maevskaia1,4

1 Blokhin National Medical Research Center of Oncology, Moscow, Russia;
2 Pirogov Russian National Research Medical University, Moscow, Russia;
3 National BioService, Saint Petersburg, Russia;
4 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
*lkoskos@mail.ru

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