Эра иммуноонкологии в онкоурологии: чего мы достигли?

1. Злокачественные новообразования в России в 2020 г. (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, А.О. Шахзадовой. М., 2021 [Zlokachestvennye novoobrazovaniia v Rossii v 2020 g. (zabolevaemost' i smertnost'). Pod red. AD Kaprina, VV Starinskogo, AO Shakhzadovoi. Moscow, 2021 (in Russian)].
2. Leilei Ai, Jian Chen, Hao Yan, et al. Drug Des Devel Ther. 2020;14:3625-49. DOI:10.2147/DDDT.S267433
3. Choueiri TK, Rini BI, Larkin JMG, et al. Avelumab plus axitinib vs sunitinib as first-line treatment of advanced renal cell carcinoma: Phase 3 study (JAVELIN Renal 101). 2017 ASCO Annual Meeting I. Abstract TPS4594.
4. Motzer R. JAVELIN Renal 101: A randomized, phase III study of avelumab + axitinib vs sunitinib as first-line treatment of advanced renal cell carcinoma (aRCC). Abstract LBA6_PR (oral presentation).
5. Motzer RJ, Penkov K, Haanen J, et al. Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019;380(12):1103-15. 
DOI:10.1056/NEJMoa1816047
6. Choueiri TK, Motzer RJ, Rini BI, et al. Updated efficacy results from the JAVELIN Renal 101 trial: First-line avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma. Ann Oncol. 2020;31(8):1030-9. DOI:10.1016/j.annonc.2020.04.010
7. Haanen J, Larkin J, Choueiri TK, et al. Efficacy of avelumab + axitinib (A + Ax) versus sunitinib (S) by IMDC risk group in advanced renal cell carcinoma (aRCC): Extended follow-up results from JAVELIN Renal 101. 2021 ASCO Annual Meeting I. Abstract 4574.
8. Von der Maase H, Hansen SW, Roberts JT, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000;17:3068-77. DOI:10.1200/JCO.2000.18.17.3068
9. Dogliotti L, Cartenì G, Siena S, et al. Gemcitabine plus cisplatin versus gemcitabine plus carboplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium: results of a randomized phase 2 trial. Eur Urol. 2007;52:134-41. DOI:10.1016/j.eururo.2006.12.029
10. De Santis M, Bellmunt J, Mead G, et al. Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: EORTC study 30986. J Clin Oncol. 2012;30:191-9. DOI:10.1200/JCO.2011.37.3571
11. Sonpavde GP, Mariani L, Lo Vullo S, et al. Impact of the Number of Cycles of Platinum Based First Line Chemotherapy for Advanced Urothelial Carcinoma. J Urol. 2018;200(6):1207-14. DOI:10.1016/j.juro.2018.07.035
12. NCCN Guidelines: Bladder Cancer, V6.2020. Available at: https://www.nccn.org/professionals/physician_gls/PDF/bladder.pdf. Accessed: 15.11.2021
13. Von der Maase H, Sengelov L, Roberts JT, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005;23(21):4602-8. DOI:10.1200/JCO.2005.07.757
14. Bajorin DF, Dodd PM, Mazumbar M, et al. Long-term survival in metastatic transitional-cell carcinoma and prognostic factors predicting outcome of therapy. J Clin Oncol. 1999;17:3173-81. DOI:10.1200/JCO.1999.17.10.3173
15. Grivas P, Monk BJ, Petrylak D, et al. Immune Checkpoint Inhibitors as Switch or Continuation Maintenance Therapy in Solid Tumors: Rationale and Current State. Target Oncol. 2019;14:505-25. DOI:10.1007/s11523-019-00665-1
16. Galluzzi L, Buqué A, Kepp O, et al. Immunological Effects of Conventional Chemotherapy and Targeted Anticancer Agents. Cancer Cell. 2015;28:690-714. DOI:10.1016/j.ccell.2015.10.012
17. De Biasi AR, Villena-Vargas J, Adusumilli PS. Cisplatin-induced antitumor immunomodulation: a review of preclinical and clinical evidence. Clin Cancer Res. 2014;20:5384-91. DOI:10.1158/1078-0432.CCR-14-1298
18. Powles T, Park SH, Voog E, et al. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020;383:1218-30. 
DOI:10.1056/NEJMoa2002788
19. Powles T, Park SH, Voog E, et al. Maintenance avelumab + best supportive care (BSC) versus BSC alone after platinum-based first-line (1L) chemotherapy in advanced urothelial carcinoma (UC): JAVELIN Bladder 100 phase III interim analysis. 2020 ASCO Annual Meeting II. Abstract LBA1 (oral presentation).
20. Grivas P, Park SH, Voog E, et al. 704MO Avelumab first-line (1L) maintenance + best supportive care (BSC) vs BSC alone with 1L chemotherapy (CTx) for advanced urothelial carcinoma (UC): Subgroup analyses from JAVELIN Bladder 100. Ann Oncol. 2020;31(Suppl. 4):S555-6. DOI:10.1016/j.annonc.2020.08.776
21. Sridhar SS, Powles T, Loriot Y, et al. Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC) in the JAVELIN Bladder 100 trial: Subgroup analysis by duration of treatment-free interval (TFI) from end of chemotherapy to start of maintenance. 2021 ASCO Annual Meeting I. Abstract 4527.
22. Powles T, Petrylak DP, Park SH, et al. Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC): Analysis of clinical and genomic subgroups from the JAVELIN Bladder 100 trial. 2021 ASCO Annual Meeting I. Abstract 4520.
23. Grivas P, Park SH, Voog E, et al. Avelumab first-line (1L) maintenance plus best supportive care (BSC) versus BSC alone for advanced urothelial carcinoma (UC): Analysis of time to end of next-line therapy in JAVELIN Bladder 100. 2021 ASCO Annual Meeting I. Abstract 4525.
24. Kelly K, Infante JR, Taylor H, et al. Safety profile of avelumab in patients with advanced solid tumors: A pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials. Cancer. 2018;124(9):2010-7. DOI:10.1002/cncr.31293
25. Fradet Y, Bellmut J, Vaughn DJ, et al. Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of >2 years of follow-up. Ann Oncol. 2019;30(6):970-6. DOI:10.1093/annonc/mdz127
26. Galsky MD, Arija JAA, Bamias A, et al. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2020;395(10236):1547-57. DOI:10.1016/S0140-6736(20)30230-0
27. Balar AV, Galsky MD, Rosenberg JE, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017;389(10064):67‑76. DOI:10.1016/S0140-6736(16)32455-2
28. Vuky J, Balar AV, Castellano D, et al. Long-Term Outcomes in KEYNOTE-052: Phase II Study Investigating First-Line Pembrolizumab in Cisplatin-Ineligible Patients With Locally Advanced or Metastatic Urothelial Cancer. J Clin Oncol. 2020;38(23):2658-66. DOI:10.1200/JCO.19.01213
29. National Comprehensive Cancer Network. Available at: www.nccn.org. Accessed: 15.11.2021
30. European Society for Medical Oncology. Available at: www.esmo.org. Accessed: 15.11.2021.
31. Bajorin D, Witjes JA, Gschwend J, et al. First results from the phase 3 CheckMate 274 trial of adjuvant nivolumab vs placebo in patients who underwent radical surgery for high-risk muscle-invasive urothelial carcinoma (MIUC). Genitourinary Cancers Symposium, 2021.
32. NCCN Guidelines Version 4.2021: Kidney Cancer.
33. Носов Д.А., Гладков О.А., Волкова М.И., и др. Практические рекомендации по лекарственному лечению почечноклеточного рака. Злокачественные опухоли: Практические рекомендации RUSSCO #3s2. 2020;11:513-22 [Nosov DA, Gladkov OA, Volkova MI, et al. Prakticheskie rekomendatsii po lekarstvennomu lecheniiu pochechnokletochnogo raka. Zlokachestvennye opukholi: Prakticheskie rekomendatsii RUSSCO #3s2. 2020;11:513-22 (in Russian)]. DOI:10.18027 / 2224-5057-2020-10-3s2-31

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1. Zlokachestvennye novoobrazovaniia v Rossii v 2020 g. (zabolevaemost' i smertnost'). Pod red. AD Kaprina, VV Starinskogo, AO Shakhzadovoi. Moscow, 2021 (in Russian).
2. Leilei Ai, Jian Chen, Hao Yan, et al. Drug Des Devel Ther. 2020;14:3625-49. DOI:10.2147/DDDT.S267433
3. Choueiri TK, Rini BI, Larkin JMG, et al. Avelumab plus axitinib vs sunitinib as first-line treatment of advanced renal cell carcinoma: Phase 3 study (JAVELIN Renal 101). 2017 ASCO Annual Meeting I. Abstract TPS4594.
4. Motzer R. JAVELIN Renal 101: A randomized, phase III study of avelumab + axitinib vs sunitinib as first-line treatment of advanced renal cell carcinoma (aRCC). Abstract LBA6_PR (oral presentation).
5. Motzer RJ, Penkov K, Haanen J, et al. Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019;380(12):1103-15. 
DOI:10.1056/NEJMoa1816047
6. Choueiri TK, Motzer RJ, Rini BI, et al. Updated efficacy results from the JAVELIN Renal 101 trial: First-line avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma. Ann Oncol. 2020;31(8):1030-9. DOI:10.1016/j.annonc.2020.04.010
7. Haanen J, Larkin J, Choueiri TK, et al. Efficacy of avelumab + axitinib (A + Ax) versus sunitinib (S) by IMDC risk group in advanced renal cell carcinoma (aRCC): Extended follow-up results from JAVELIN Renal 101. 2021 ASCO Annual Meeting I. Abstract 4574.
8. Von der Maase H, Hansen SW, Roberts JT, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000;17:3068-77. DOI:10.1200/JCO.2000.18.17.3068
9. Dogliotti L, Cartenì G, Siena S, et al. Gemcitabine plus cisplatin versus gemcitabine plus carboplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium: results of a randomized phase 2 trial. Eur Urol. 2007;52:134-41. DOI:10.1016/j.eururo.2006.12.029
10. De Santis M, Bellmunt J, Mead G, et al. Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: EORTC study 30986. J Clin Oncol. 2012;30:191-9. DOI:10.1200/JCO.2011.37.3571
11. Sonpavde GP, Mariani L, Lo Vullo S, et al. Impact of the Number of Cycles of Platinum Based First Line Chemotherapy for Advanced Urothelial Carcinoma. J Urol. 2018;200(6):1207-14. DOI:10.1016/j.juro.2018.07.035
12. NCCN Guidelines: Bladder Cancer, V6.2020. Available at: https://www.nccn.org/professionals/physician_gls/PDF/bladder.pdf. Accessed: 15.11.2021
13. Von der Maase H, Sengelov L, Roberts JT, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005;23(21):4602-8. DOI:10.1200/JCO.2005.07.757
14. Bajorin DF, Dodd PM, Mazumbar M, et al. Long-term survival in metastatic transitional-cell carcinoma and prognostic factors predicting outcome of therapy. J Clin Oncol. 1999;17:3173-81. DOI:10.1200/JCO.1999.17.10.3173
15. Grivas P, Monk BJ, Petrylak D, et al. Immune Checkpoint Inhibitors as Switch or Continuation Maintenance Therapy in Solid Tumors: Rationale and Current State. Target Oncol. 2019;14:505-25. DOI:10.1007/s11523-019-00665-1
16. Galluzzi L, Buqué A, Kepp O, et al. Immunological Effects of Conventional Chemotherapy and Targeted Anticancer Agents. Cancer Cell. 2015;28:690-714. DOI:10.1016/j.ccell.2015.10.012
17. De Biasi AR, Villena-Vargas J, Adusumilli PS. Cisplatin-induced antitumor immunomodulation: a review of preclinical and clinical evidence. Clin Cancer Res. 2014;20:5384-91. DOI:10.1158/1078-0432.CCR-14-1298
18. Powles T, Park SH, Voog E, et al. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020;383:1218-30. 
DOI:10.1056/NEJMoa2002788
19. Powles T, Park SH, Voog E, et al. Maintenance avelumab + best supportive care (BSC) versus BSC alone after platinum-based first-line (1L) chemotherapy in advanced urothelial carcinoma (UC): JAVELIN Bladder 100 phase III interim analysis. 2020 ASCO Annual Meeting II. Abstract LBA1 (oral presentation).
20. Grivas P, Park SH, Voog E, et al. 704MO Avelumab first-line (1L) maintenance + best supportive care (BSC) vs BSC alone with 1L chemotherapy (CTx) for advanced urothelial carcinoma (UC): Subgroup analyses from JAVELIN Bladder 100. Ann Oncol. 2020;31(Suppl. 4):S555-6. DOI:10.1016/j.annonc.2020.08.776
21. Sridhar SS, Powles T, Loriot Y, et al. Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC) in the JAVELIN Bladder 100 trial: Subgroup analysis by duration of treatment-free interval (TFI) from end of chemotherapy to start of maintenance. 2021 ASCO Annual Meeting I. Abstract 4527.
22. Powles T, Petrylak DP, Park SH, et al. Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC): Analysis of clinical and genomic subgroups from the JAVELIN Bladder 100 trial. 2021 ASCO Annual Meeting I. Abstract 4520.
23. Grivas P, Park SH, Voog E, et al. Avelumab first-line (1L) maintenance plus best supportive care (BSC) versus BSC alone for advanced urothelial carcinoma (UC): Analysis of time to end of next-line therapy in JAVELIN Bladder 100. 2021 ASCO Annual Meeting I. Abstract 4525.
24. Kelly K, Infante JR, Taylor H, et al. Safety profile of avelumab in patients with advanced solid tumors: A pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials. Cancer. 2018;124(9):2010-7. DOI:10.1002/cncr.31293
25. Fradet Y, Bellmut J, Vaughn DJ, et al. Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of >2 years of follow-up. Ann Oncol. 2019;30(6):970-6. DOI:10.1093/annonc/mdz127
26. Galsky MD, Arija JAA, Bamias A, et al. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2020;395(10236):1547-57. DOI:10.1016/S0140-6736(20)30230-0
27. Balar AV, Galsky MD, Rosenberg JE, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017;389(10064):67‑76. DOI:10.1016/S0140-6736(16)32455-2
28. Vuky J, Balar AV, Castellano D, et al. Long-Term Outcomes in KEYNOTE-052: Phase II Study Investigating First-Line Pembrolizumab in Cisplatin-Ineligible Patients With Locally Advanced or Metastatic Urothelial Cancer. J Clin Oncol. 2020;38(23):2658-66. DOI:10.1200/JCO.19.01213
29. National Comprehensive Cancer Network. Available at: www.nccn.org. Accessed: 15.11.2021
30. European Society for Medical Oncology. Available at: www.esmo.org. Accessed: 15.11.2021.
31. Bajorin D, Witjes JA, Gschwend J, et al. First results from the phase 3 CheckMate 274 trial of adjuvant nivolumab vs placebo in patients who underwent radical surgery for high-risk muscle-invasive urothelial carcinoma (MIUC). Genitourinary Cancers Symposium, 2021.
32. NCCN Guidelines Version 4.2021: Kidney Cancer.
33. Nosov DA, Gladkov OA, Volkova MI, et al. Prakticheskie rekomendatsii po lekarstvennomu lecheniiu pochechnokletochnogo raka. Zlokachestvennye opukholi: Prakticheskie rekomendatsii RUSSCO #3s2. 2020;11:513-22 (in Russian). 
DOI:10.18027 / 2224-5057-2020-10-3s2-31

Эксперты:
Алексеев Борис Яковлевич – д-р мед. наук, проф., зам. ген. дир. по науке ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава России;
Калпинский Алексей Сергеевич – канд. мед. наук, ст. науч. сотр. отд. опухолей репродуктивных и мочевыводящих органов Московского научно-исследовательского онкологического института им. П.А. Герцена – филиала ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава России, Москва, Россия;
Матвеев Всеволод Борисович – чл.-кор. РАН, д-р мед. наук, проф., зав. отд-нием онкоурологии, зам. дир. по научной и инновационной работе ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» 
Минздрава России, Москва, Россия;
Гшвенд Юрген (Jürgen Gschwend) – проф., Немецкий кардиологический центр, Мюнхен, Германия;
Носов Дмитрий Александрович – проф. РАН, д-р мед. наук, зав. онкологическим отд-нием противоопухолевой лекарственной терапии (с дневным стационаром) ФГБУ «Центральная клиническая больница с поликлиникой» Управления делами Президента РФ, Москва, Россия

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Experts:
Boris Ya. Alekseev – D. Sci. (Med.), Prof., National Medical Research Center for Radiology, Moscow, Russia;
Alexey S. Kalpinsky – Cand. Sci. (Med.), Herzen Moscow Scientifuc Research Institute of Oncology – branch of the National Medical Research Center for Radiology, Moscow, Russia;
Vsevolod B. Matveev – D. Sci. (Med.), Prof., Corr. Memb. RAS, Blokhin National Medical Research Center of Oncology, Moscow, Russia;
Jürgen Gschwend – M.D., Prof., German Cardiological Center, Munich, Germany;
Dmitrii A. Nosov – D. Sci. (Med.), Prof. RAS, Central Clinical Hospital of the Administrative Directorate of the President of the Russian Federation, Moscow, Russia