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Перспективы развития адъювантной терапии при немелкоклеточном раке легкого
Лактионов К.К., Казаков А.М., Реутова Е.В. и др. Перспективы развития адъювантной терапии при немелкоклеточном раке легкого. Современная Онкология. 2020; 22 (3): 85–87. DOI: 10.26442/18151434.2020.3.200339
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Laktionov K.K., Kazakov A.M., Reutova E.V. et al. Prospects for the development of adjuvant therapy for non-small cell lung cancer. Journal of Modern Oncology. 2020; 22 (3): 85–87. DOI: 10.26442/18151434.2020.3.200339
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Аннотация
В настоящее время стандартным подходом для немелкоклеточного рака легкого (НМРЛ) II–IIIA стадии, а также стадии IB при высоком риске рецидива, после полной резекции является адъювантная химиотерапия. Выигрыш в 5-летней выживаемости при применении данного подхода составляет около 5%, а риск рецидива снижается от 11 до 15% в зависимости от стадии. Тем не менее частота рецидива в течение 5 лет после операции и адъювантной химиотерапии при НМРЛ IB–IIIА стадии составляет до 70%. Данное обстоятельство требует поиска новых решений. Эффективность и профиль безопасности таргетных препаратов при метастатическом НМРЛ позволяют предположить возможность их использования в качестве адъювантной терапии при ранних стадиях заболевания. Данный подход активно изучался у пациентов с наличием мутации в гене EGFR, и наиболее перспективными оказались результаты исследования ADAURA, в котором в качестве адъювантной терапии изучалось применение осимертиниба, ингибитора тирозинкиназы EGFR III поколения. Применение адъювантной таргетной терапии у ALKm-пациентов на данный момент менее изучено, ее эффективность будет определена по мере получения результатов исследований ALINA и ALCHEMIST.
Ключевые слова: немелкоклеточный рак легкого, адъювантная таргетная терапия.
Ключевые слова: немелкоклеточный рак легкого, адъювантная таргетная терапия.
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The standard approach for stage IB and II–IIIA non-small cell lung cancer (NSCLC), associated with the high risk of relapse, after total lung resection is adjuvant chemotherapy, nowadays. The 5-year survival benefit for this approach is about 5%, and the risk of relapse reduces from 11 to 15%, depending on the stage. However, the relapse rate within 5 years after surgery and adjuvant chemotherapy in stage IB–IIIA NSCLC is up to 70%. This fact requires the search for new solutions. The efficacy and safety profile of targeted drugs in metastatic NSCLC show the possibility to use them as adjuvant therapy in the early stages of the disease. This approach was actively studied in patients with mutations in the EGFR gene, and the most promising were the results of the ADAURA trial, which had been studied the use of Osimertinib, a third-generation EGFR tyrosine kinase inhibitor, as adjuvant therapy. The use of adjuvant targeted therapy in ALK-positive patients is currently less studied and its efficacy will be determined as the results of the ALINA and ALCHEMIST trials are obtained.
Key words: non-small cell lung cancer, adjuvant targeted therapy.
Полный текст
Список литературы
1. Pignon J-P, Tribodet H, Scagliotti GV et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol 2008; 26 (21): 3552–9. DOI: 10.1200/JCO.2007.13.9030
2. Ye T, Chen H. 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
3. Kelly K, Altorki NK, Eberhardt WEE 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
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. 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
6. 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.
7. Ramalingam SS, Vansteenkiste J, Planchard D et al. Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC. January 2, 2020. N Engl J Med 2020; 382: 41–50. DOI: 10.1056/NEJMoa1913662
8. Zhang H. Osimertinib making a breakthrough in lung cancer targeted therapy. Onco Targets Ther 2016; 9: 5489–93. DOI: 10.2147/OTT.S114722
9. Herbst RS, Tsuboi M, John T. Osimertinib as adjuvant therapy in patients (pts) with stageIB–IIIA EGFR mutation positive (EGFRm) NSCLC after complete tumor resection: ADAURA. J Clin Oncol 2020; 38.
10. Tianli Zhang, Bing Wan, Yuan Zhao, et al. Treatment of uncommon EGFR mutations in non-small cell lung cancer: new evidence and treatment. Transl Lung Cancer Res 2019; 8 (3): 302–16. DOI: 10.21037/tlcr.2019.04.12
11. Yang JC-H, Sequist LV, Geater SL et al. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol 2015; 16 (7): 830–8. DOI: 10.1016/S1470-2045 (15)00026-1
12. Jang Ho Cho, Sung Hee Lim, Ho Jung An et al. Osimertinib for Patients With Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Multicenter, Open-Label, Phase II Trial (KCSG-LU15-09). J Clin Oncol 2020; 38 (5): 488–95. DOI: 10.1200/JCO.19.00931
13. Solomon BJ, Ahn JS, Barlesi F et al. ALINA: A phase III study of alectinib versus chemotherapy as adjuvant therapy in patients with stage IB–IIIA anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC). J Clin Oncol 2019; 37. DOI: 10.1200/JCO.2019.37.15_suppl.TPS8569 Journal of Clinical Oncology 37, no. 15_suppl
14. Tabbò F, Novello S. Expanding anaplastic lymphoma kinase therapeutic indication to early stage non-small cell lung cancer. Transl Lung Cancer Res 2019; 8 (Suppl. 3): S290–S297. DOI: 10.21037/tlcr.2019.07.07
2. Ye T, Chen H. 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
3. Kelly K, Altorki NK, Eberhardt WEE 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
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. 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
6. 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.
7. Ramalingam SS, Vansteenkiste J, Planchard D et al. Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC. January 2, 2020. N Engl J Med 2020; 382: 41–50. DOI: 10.1056/NEJMoa1913662
8. Zhang H. Osimertinib making a breakthrough in lung cancer targeted therapy. Onco Targets Ther 2016; 9: 5489–93. DOI: 10.2147/OTT.S114722
9. Herbst RS, Tsuboi M, John T. Osimertinib as adjuvant therapy in patients (pts) with stageIB–IIIA EGFR mutation positive (EGFRm) NSCLC after complete tumor resection: ADAURA. J Clin Oncol 2020; 38.
10. Tianli Zhang, Bing Wan, Yuan Zhao, et al. Treatment of uncommon EGFR mutations in non-small cell lung cancer: new evidence and treatment. Transl Lung Cancer Res 2019; 8 (3): 302–16. DOI: 10.21037/tlcr.2019.04.12
11. Yang JC-H, Sequist LV, Geater SL et al. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol 2015; 16 (7): 830–8. DOI: 10.1016/S1470-2045 (15)00026-1
12. Jang Ho Cho, Sung Hee Lim, Ho Jung An et al. Osimertinib for Patients With Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Multicenter, Open-Label, Phase II Trial (KCSG-LU15-09). J Clin Oncol 2020; 38 (5): 488–95. DOI: 10.1200/JCO.19.00931
13. Solomon BJ, Ahn JS, Barlesi F et al. ALINA: A phase III study of alectinib versus chemotherapy as adjuvant therapy in patients with stage IB–IIIA anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC). J Clin Oncol 2019; 37. DOI: 10.1200/JCO.2019.37.15_suppl.TPS8569 Journal of Clinical Oncology 37, no. 15_suppl
14. Tabbò F, Novello S. Expanding anaplastic lymphoma kinase therapeutic indication to early stage non-small cell lung cancer. Transl Lung Cancer Res 2019; 8 (Suppl. 3): S290–S297. DOI: 10.21037/tlcr.2019.07.07
________________________________________________
1. Pignon J-P, Tribodet H, Scagliotti GV et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol 2008; 26 (21): 3552–9. DOI: 10.1200/JCO.2007.13.9030
2. Ye T, Chen H. 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
3. Kelly K, Altorki NK, Eberhardt WEE 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
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. 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
6. 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.
7. Ramalingam SS, Vansteenkiste J, Planchard D et al. Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC. January 2, 2020. N Engl J Med 2020; 382: 41–50. DOI: 10.1056/NEJMoa1913662
8. Zhang H. Osimertinib making a breakthrough in lung cancer targeted therapy. Onco Targets Ther 2016; 9: 5489–93. DOI: 10.2147/OTT.S114722
9. Herbst RS, Tsuboi M, John T. Osimertinib as adjuvant therapy in patients (pts) with stageIB–IIIA EGFR mutation positive (EGFRm) NSCLC after complete tumor resection: ADAURA. J Clin Oncol 2020; 38.
10. Tianli Zhang, Bing Wan, Yuan Zhao, et al. Treatment of uncommon EGFR mutations in non-small cell lung cancer: new evidence and treatment. Transl Lung Cancer Res 2019; 8 (3): 302–16. DOI: 10.21037/tlcr.2019.04.12
11. Yang JC-H, Sequist LV, Geater SL et al. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol 2015; 16 (7): 830–8. DOI: 10.1016/S1470-2045 (15)00026-1
12. Jang Ho Cho, Sung Hee Lim, Ho Jung An et al. Osimertinib for Patients With Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Multicenter, Open-Label, Phase II Trial (KCSG-LU15-09). J Clin Oncol 2020; 38 (5): 488–95. DOI: 10.1200/JCO.19.00931
13. Solomon BJ, Ahn JS, Barlesi F et al. ALINA: A phase III study of alectinib versus chemotherapy as adjuvant therapy in patients with stage IB–IIIA anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC). J Clin Oncol 2019; 37. DOI: 10.1200/JCO.2019.37.15_suppl.TPS8569 Journal of Clinical Oncology 37, no. 15_suppl
14. Tabbò F, Novello S. Expanding anaplastic lymphoma kinase therapeutic indication to early stage non-small cell lung cancer. Transl Lung Cancer Res 2019; 8 (Suppl. 3): S290–S297. DOI: 10.21037/tlcr.2019.07.07
Авторы
К.К. Лактионов*1,2, А.М. Казаков1, Е.В. Реутова1, М.С. Ардзинба1, А.Л. Арзуманян1
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
*lkoskos@mail.ru
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
*lkoskos@mail.ru
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Konstantin K. Laktionov*1,2, Aleksei M. Kazakov1, Elena V. Reutova1, Merab S. Ardzinba1, Alla L. Arzumanian1
1 Blokhin National Medical Research Center of Oncology, Moscow, Russia;
2 Pirogov Russian National Research Medical University, Moscow, Russia
*lkoskos@mail.ru
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