Применение комбинации атезолизумаба и химиотерапии в 1-й линии метастатического мелкоклеточного рака легкого. Клинический опыт
Применение комбинации атезолизумаба и химиотерапии в 1-й линии метастатического мелкоклеточного рака легкого. Клинический опыт
Огнерубов Н.А., Антипова Т.С. Применение комбинации атезолизумаба и химиотерапии в 1-й линии метастатического мелкоклеточного рака легкого. Клинический опыт. Современная Онкология. 2021; 23 (2): 292–298. DOI: 10.26442/18151434.2021.2.200965
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Ognerubov NA, Antipova TS. The use of atezolizumab in combination with chemotherapy in first-line of metastatic small cell lung cancer. Case report. Journal of Modern Oncology. 2021; 23 (2): 292–298.
DOI: 10.26442/18151434.2021.2.200965
Применение комбинации атезолизумаба и химиотерапии в 1-й линии метастатического мелкоклеточного рака легкого. Клинический опыт
Огнерубов Н.А., Антипова Т.С. Применение комбинации атезолизумаба и химиотерапии в 1-й линии метастатического мелкоклеточного рака легкого. Клинический опыт. Современная Онкология. 2021; 23 (2): 292–298. DOI: 10.26442/18151434.2021.2.200965
________________________________________________
Ognerubov NA, Antipova TS. The use of atezolizumab in combination with chemotherapy in first-line of metastatic small cell lung cancer. Case report. Journal of Modern Oncology. 2021; 23 (2): 292–298.
DOI: 10.26442/18151434.2021.2.200965
Обоснование. Рак легкого (РЛ) занимает лидирующее положение среди злокачественных опухолей в мире, на его долю приходится 11,4% злокачественных новообразований. В 2020 г. в мире выявлен 2 206 771 новый случай РЛ и 1 796 144 смерти от него. Среди различных гистологических вариантов мелкоклеточный РЛ (МКРЛ) является самым неблагоприятным. Он считается высокочувствительным к химиотерапии. Несмотря на определенные успехи в терапии этого заболевания, результаты лечения остаются малоутешительными. В последние годы применение ингибиторов контрольных точек иммунного ответа обеспечило значимый контроль течения заболевания. Цель. Показать эффективность применения атезолизумаба в комбинации с химиотерапией при метастатическом МКРЛ. Материалы и методы. Под наблюдением находился пациент 76 лет с диагнозом: рак левого легкого, ст. IVА T4N3M1b, метастазы в надключичный лимфоузел справа, экссудативный плеврит слева. При гистологическом исследовании установлен МКРЛ. Метастазы в головной мозг не выявлены. ECOG 0. Результаты. Пациенту проводили лечение по схеме атезолизумаб 1200 мг вместе с карбоплатином 5 AUC и этопозидом 100 мг/м2 1–3-й день в количестве 4 циклов с последующим переходом на поддерживающую терапию атезолизумабом 1200 мг каждый 21-й день. Больной получил 21 введение на протяжении 14 мес. Оценка эффекта лечения осуществлялась с помощью комбинированной позитронно-эмиссионной и рентгеновской компьютерной томографии с 18F-фтордезоксиглюкозой. В результате проведенного лечения через 7 мес получена полная клиническая и морфо-метаболическая регрессия опухоли, которая сохраняется на протяжении всего периода лечения. Из нежелательных явлений отмечались анемия 2-й степени и сенсорная нейропатия 1-й степени. Иммуноопосредованных побочных реакций не наблюдалось. Заключение. Добавление атезолизумаба к химиотерапии этопозид + карбоплатин в качестве терапии 1-й линии распространенного МКРЛ обеспечивает длительную общую и безрецидивную выживаемость, сохраняя при этом удовлетворительное качество жизни пациентов и приемлемую переносимость препаратов.
Background. Lung cancer (LC) occupies a leading position among malignant tumors in the world, it accounts for 11.4% of the total malignant neoplasms. In 2020, there were 2 206 771 new cases of LC and 1 796 144 deaths worldwide. Among the histological variants, small cell LC (SCLC) has the most unfavorable outcomes. This variant is considered highly sensitive to chemotherapy. Despite some successes in the treatment of this disease, the results of treatment remain problematical. In recent years, the use of immune checkpoint inhibitors has provided significant control of the course of the disease. Aim. To show the efficacy of atezolizumab in combination with chemotherapy in patients with metastatic SCLC.
Materials and methods. A 76-year-old patient with left lung cancer, IVA T4N3M1b, the right supraclavicular lymph node metastases, exudative pleuritis of the left lung was under observation. The histological investigation showed SCLC. Brain metastases were not detected. ECOG 0. Results. The patient was treated using atezolizumab 1200 mg in combination with carboplatin 5 AUC and etoposide 100 mg/m2 on days 1, 2, 3 for four cycles, followed by a maintenance therapy regimen with atezolizumab 1200 mg every 21 days. The patient received 21 injections during 14 months. The assessment of treatment effect was evaluated using combined 18F-fluorodeoxyglucose positron emission and X-ray computed tomography. As a result of the treatment, after 7 months, a complete clinical and morpho-metabolic regression of the tumor was reached, which persisted throughout the period of the treatment. Among the adverse events were detected grade 2 anemia and first-stage sensory neuropathy. No immune-related adverse events were observed. Conclusion. The addition of atezolizumab to etoposide + carboplatin as the first-line therapy for extensive-stage SCLC provides the long-term overall and disease-free survival with achieving the satisfactory quality of life in patients and acceptable drug tolerance.
Keywords: small cell lung cancer, PD-1/PD-L1 checkpoint inhibitors, atezolizumab, combined positron emission and X-ray computed tomography
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15. Eckardt JR, Von Pawel J, Pujol JL, et al. Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol. 2007;25:2086-92. DOI:10.1200/JCO.2006.08.3998
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19. Schultheis AM, Scheel AH, Ozretić L, et al. PD-L1 expression in small cell neuroendocrine carcinomas. Eur J Cancer. 2015;51:421-6. DOI:10.1016/j.ejca.2014.12.006
20. Alexandrov LB, Nik-Zainal S, Wedge DC, et al. Signatures of mutational processes in human cancer. Nature. 2013;500:415-21. DOI:10.1038/nature12477
21. Pelosof LC, Gerber DE. Paraneoplastic syndromes: An approach to diagnosis and treatment. Mayo Clin Proc. 2010;85:838-54. DOI:10.4065/mcp.2010.0099
22. Pujol JL, Greillier L, Audigier-Valette C, et al. A randomized non-comparative phase II study of anti-programmed cell death-ligand 1 atezolizumab or chemotherapy as second-line therapy in patients with small cell lung cancer: Results from the IFCT-1603 trial. J Thorac Oncol. 2019;14:903-13. DOI:10.1016/j.jtho.2019.01.008
23. Ready N, Farago AF, de Braud F, et al. Third-Line Nivolumab Monotherapy in Recurrent SCLC: CheckMate 032. J Thorac Oncol. 2019;14:237-44. DOI:10.1016/j.jtho.2018.10.003
24. Liu SV, Reck M, Mansfield AS, et al. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021;39(6):619-30. DOI:10.1200/JCO.20.01055
25. Reck M, Liu SV, Mansfield AS, et al. IMpower133: Updated overall survival (OS) analysis of first-line (1L) atezolizumab (atezo) + carboplatin + etoposide in extensive-stage SCLC (ES-SCLC). Ann Oncol. 2019;30(Suppl. 5):V710-1. DOI:10.1093/annonc/mdz264
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27. Facchinetti F, Di Maio M, Tiseo M. Adding PD-1/PD-L1 Inhibitors to Chemotherapy for the First-Line Treatment of Extensive Stage Small Cell Lung Cancer (SCLC): A Meta-Analysis of Randomized Trials. Cancers (Basel). 2020;12(9):2645. DOI:10.3390/cancers12092645
28. Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab +/− tremelimumab + platinum-etoposide in first-line extensive-stage SCLC (ES-SCLC): Updated results from the phase III CASPIAN study. J Clin Oncol. 2020;38:9002. DOI:10.1200/JCO.2020.38.15_suppl.9002
29. Rudin CM, Awad MM, Navarro A, et al. Pembrolizumab or placebo plus etoposide and platinum as first-line therapy for extensive-stage small-cell lung cancer. J Clin Oncol. 2020;38:2369-79. DOI:10.1200/JCO.20.00793
30. Rudin CM, Awad MM, Navarro A, et al. KEYNOTE-604: Pembrolizumab (pembro) or placebo plus etoposide and platinum (EP) as first-line therapy for extensive-stage (ES) small-cell lung cancer (SCLC) J Clin Oncol. 2020;38:9001. DOI:10.1200/JCO.2020.38.15_suppl.9001
________________________________________________
1. Globacan 2018. Available at: https://gco.iarc.fr// Accessed: 15.03.2021.
2. Ed. AD Kaprin, VV Starinskii, AO Shakhzadova. Malignant neoplasms in Russia in 2019 (morbidity and mortality). Moscow: P. Hertsen Moscow Oncology Research Institute – the branch of National Medical Research Radiological Centre, 2020 (in Russian)
3. Van Meerbeeck JP, Fennell DA, De Ruysscher DK. Small-cell lung cancer. Lancet. 2011;378:1741-55. DOI:10.1016/S0140-6736(11)60165-7
4. Bernhardt EB, Jalal SI. Small cell lung cancer. Cancer Treat Res. 2016;170:301-22. DOI:10.1007/978-3-319-40389-2_14
5. Lopez-Chavez A, Sandler A. Systemic issues in small cell lung cancer. Curr Probl Cancer. 2012;36(3):131-55. DOI:10.1016/j.currproblcancer.2012.03.004
6. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Small Cell Lung Cancer (Version 1.2019), 2019. Available at: https://tomocenter.com.ua/wp-content/uploads/small-cell-lung-cancer.pdf. Accessed: 20.03.2021.
7. Armstrong SA, Liu SV. Dashing decades of defeat: Long anticipated advances in the first-line treatment of extensive-stage small cell lung cancer. Curr Oncol Reports. 2020;22:20. DOI:10.1007/s11912-020-0887-y
8. Rossi A, Di Maio M, Chiodini P, et al. Carboplatin- or cisplatin-based chemotherapy in first-line treatment of small-cell lung cancer: The COCIS meta-analysis of individual patient data. J Clin Oncol. 2012;30:1692-8. DOI:10.1200/JCO.2011.40.4905
9. Foster NR, Renfro LA, Schild SE, et al. Multitrial evaluation of progression-free survival as a surrogate end point for overall survival in first-line extensive-stage small-cell lung cancer. J Thorac Oncol. 2015;10:1099-106. DOI:10.1097/JTO.0000000000000548
10. Horn L, Mansfield AS, Szczęsna A, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018;379:2220-9. DOI:10.1056/NEJMoa1809064
11. Antonia SJ, Lopez-Martin JA, Bendell J, et al. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): A multicentre, open-label, phase 1/2 trial. Lancet Oncol. 2016;17:883-95. DOI:10.1016/S1470-2045(16)30098-5
12. Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum–etoposide versus platinum – etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): A randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394:P1929-39. DOI:10.1016/S0140-6736(19)32222-6
13. TECENTRIQ (Atezolizumab) [Summary of Product Characteristics]. Grenzach-Wyhlen, Germany, Roche Registration GmbH, 2019.
14. Ott PA, Elez E, Hiret S, et al. Pembrolizumab in patients with extensive-stage small-cell lung cancer: Results from the phase Ib KEYNOTE-028 study. J Clin Oncol. 2017;35:3823-9. DOI:10.1200/JCO.2017.72.5069
15. Eckardt JR, Von Pawel J, Pujol JL, et al. Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol. 2007;25:2086-92. DOI:10.1200/JCO.2006.08.3998
16. Schmittel A, Sebastian M, Fischer von Weikersthal L, et al. A German multicenter, randomized phase III trial comparing irinotecan-carboplatin with etoposide-carboplatin as first-line therapy for extensive-disease small-cell lung cancer. Ann Oncol. 2011;22:1798-804. DOI:10.1093/annonc/mdq652
17. Higgins KA, Curran WJ Jr., Liu SV, et al. Patterns of Disease Progression after Carboplatin/Etoposide + Atezolizumab in Extensive-Stage Small-Cell Lung Cancer (ES-SCLC). Int J Radiat Oncol Biol Phys. 2020;108(5):1398. DOI:10.1016/j.ijrobp.2020.09.020
18. Chen H, Horita N, Ito K, et al. Affiliations expand Systematic review of first-line chemotherapy for chemo-naive extensive-stage small-cell lung cancer: network meta-analysis. Ther Adv Med Oncol. 2020;12:1758835920965841. DOI:10.1177/1758835920965841
19. Schultheis AM, Scheel AH, Ozretić L, et al. PD-L1 expression in small cell neuroendocrine carcinomas. Eur J Cancer. 2015;51:421-6. DOI:10.1016/j.ejca.2014.12.006
20. Alexandrov LB, Nik-Zainal S, Wedge DC, et al. Signatures of mutational processes in human cancer. Nature. 2013;500:415-21. DOI:10.1038/nature12477
21. Pelosof LC, Gerber DE. Paraneoplastic syndromes: An approach to diagnosis and treatment. Mayo Clin Proc. 2010;85:838-54. DOI:10.4065/mcp.2010.0099
22. Pujol JL, Greillier L, Audigier-Valette C, et al. A randomized non-comparative phase II study of anti-programmed cell death-ligand 1 atezolizumab or chemotherapy as second-line therapy in patients with small cell lung cancer: Results from the IFCT-1603 trial. J Thorac Oncol. 2019;14:903-13. DOI:10.1016/j.jtho.2019.01.008
23. Ready N, Farago AF, de Braud F, et al. Third-Line Nivolumab Monotherapy in Recurrent SCLC: CheckMate 032. J Thorac Oncol. 2019;14:237-44. DOI:10.1016/j.jtho.2018.10.003
24. Liu SV, Reck M, Mansfield AS, et al. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021;39(6):619-30. DOI:10.1200/JCO.20.01055
25. Reck M, Liu SV, Mansfield AS, et al. IMpower133: Updated overall survival (OS) analysis of first-line (1L) atezolizumab (atezo) + carboplatin + etoposide in extensive-stage SCLC (ES-SCLC). Ann Oncol. 2019;30(Suppl. 5):V710-1. DOI:10.1093/annonc/mdz264
26. Chung HC, Piha-Paul SA, Lopez-Martin J, et al. Pembrolizumab After Two or More Lines of Previous Therapy in Patients With Recurrent or Metastatic SCLC: Results From the KEYNOTE-028 and KEYNOTE-158 Studies. J Thorac Oncol. 2020;15:618-27. DOI:10.1016/j.jtho.2019.12.109
27. Facchinetti F, Di Maio M, Tiseo M. Adding PD-1/PD-L1 Inhibitors to Chemotherapy for the First-Line Treatment of Extensive Stage Small Cell Lung Cancer (SCLC): A Meta-Analysis of Randomized Trials. Cancers (Basel). 2020;12(9):2645. DOI:10.3390/cancers12092645
28. Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab +/− tremelimumab + platinum-etoposide in first-line extensive-stage SCLC (ES-SCLC): Updated results from the phase III CASPIAN study. J Clin Oncol. 2020;38:9002. DOI:10.1200/JCO.2020.38.15_suppl.9002
29. Rudin CM, Awad MM, Navarro A, et al. Pembrolizumab or placebo plus etoposide and platinum as first-line therapy for extensive-stage small-cell lung cancer. J Clin Oncol. 2020;38:2369-79. DOI:10.1200/JCO.20.00793
30. Rudin CM, Awad MM, Navarro A, et al. KEYNOTE-604: Pembrolizumab (pembro) or placebo plus etoposide and platinum (EP) as first-line therapy for extensive-stage (ES) small-cell lung cancer (SCLC) J Clin Oncol. 2020;38:9001. DOI:10.1200/JCO.2020.38.15_suppl.9001
Авторы
Н.А. Огнерубов*1,2, Т.С. Антипова3
1 ФГБОУ ВО «Тамбовский государственный университет им. Г.Р. Державина», Тамбов, Россия;
2 ГБУЗ «Тамбовский областной онкологический клинический диспансер», Тамбов, Россия;
3 ООО «ПЭТ-Технолоджи», Центр ядерной медицины, Тамбов, Россия
*ognerubov_n.a@mail.ru
________________________________________________
Nikolai A. Ognerubov*1,2, Tatyana S. Antipova3
1 Derzhavin Tambov State University, Tambov, Russia;
2 Tambov Regional Oncological Clinical Dispensary, Tambov, Russia;
3 “PET-Technoligy” Ltd, Nuclear Medicine Center, Tambov, Russia
*ognerubov_n.a@mail.ru