Abstract
Significant number of patients with early and locally advanced non-small cell lung cancer (NSCLC) develops relapses after surgical treatment. Effective medical therapy preventing relapses in operable NSCLC is apparently still urgently needed. Immunotherapy with immune checkpoint inhibitors has become the main treatment for progressive NSCLC. Neoadjuvant checkpoint blockade is well tolerated without causing excessive toxicity and increased postoperative complications and mortality rates. Phase II clinical trials have shown promising results, and prospective phase III trials are currently underway. The role of adjuvant immunotherapy with checkpoint inhibitors is unclear and remains the subject of numerous prospective studies.
References
Siegel RL, Miller KD, Jemal A. Cancer Statistics 2017 // CA Cancer J Clin. 2017;67:7–30. doi:10.3322/caac.21387
Goldstraw P, Chansky K, Crowley J et al. The IASLC lung cancer staging project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification of lung cancer // J Thorac Oncol. 2016;11:39–51. doi:10.1016/j.jtho.2015.09.009
Лазутин Ю.Н., Пыльцин С.П., Харитонова А.П. Современное состояние проблемы неоадьювантной химиотерапии немелкоклеточного рака легкого (НМРЛ) // Злокачественные опухоли. 2014;3(10):22–29 [Lazutin YuN, Pyltsin SP, Kharitonova AP. Current state of the problem of neoadjuvant chemotherapy for non-small cell lung cancer (NSCLC) // Zlokachestvennye opukholi. 2014;3(10):22–29 (In Russ.)].
Сагакянц А.Б. Объединенный иммунологический форум: современные направления развития фундаментальной и прикладной онкоиммунологии (Новосибирск, 2019) // Южно-Российский онкологический журнал. 2020;1(2):36–45. doi:10.37748/2687-0533-2020-1-2-5 [Sagakyants A.B. United immunological forum: current trends in the development of fundamental and applied oncoimmunology (Novosibirsk, 2019) // Yuzhno-Rossiiskii onkologicheskii zhurnal. 2020;1(2):36–45 (In Russ.)]. doi:10.37748/2687-0533-2020-1-2-5
Sharma P, Allison JP. The future of immune checkpoint therapy // Science. 2015;348(6230):56–61. doi:10.1126/science.aaa8172
Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy // Nat Rev Cancer. 2012;12(4):252–64. doi:10.1038/nrc3239
Darvin P, Toor SM, Sasidharan Nair V et al. Immune checkpoint inhibitors: recent progress and potential biomarkers // Exp Mol Med. 2018;50(12). doi:10.1038/s12276-018-0191-1
Antonia SJ, Villegas A, Daniel D et al. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer // N Engl J Med. 2017;377(20):1919–29. doi:10.1056/NEJMoa1709937
Mok TSK, Wu YL, Kudaba I et al. Pembrolizumab versus chemotherapy for previously untreated, PDL1-expressing, locally advanced or metastatic nonsmall-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial // Lancet. 2019;393(10183):1819–30. doi:10.1016/S0140-6736(18)32409-7
Kazandjian D, Suzman DL, Blumenthal G et al. FDA approval summary: nivolumab for the treatment of metastatic non-small cell lung cancer with progression on or after platinum-based chemotherapy // Oncologist. 2016;21(5):634–42. doi:10.1634/theoncologist.2015-0507
Walker LS, Sansom DM. The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses // Nat Rev Immunol. 2011;11:852–63. doi:10.1038/nri3108
Keir ME, Butte MJ, Freeman GJ et al. PD-1 and its ligands in tolerance and immunity // Annu Rev Immunol 2008;26:677–704. doi:10.1146/annurev.immunol.26.021607.090331
Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade // Science. 1996;271:1734–6. doi:10.1126/science.271.5256.1734
Hurwitz AA, Yu TFY, Leach DR et al. CTLA-4 blockade synergizes with tumor-derived granulocyte-macrophage colony-stimulating factor for treatment of an experimental mammary carcinoma // Proc Natl Acad Sci USA. 1998;95(17):10067–71. doi:10.1073/pnas.95.17.10067
Stephen Hodi F, O’Day SJ, McDermott DF et al. Improved survival with ipilimumab in patients with metastatic melanoma // N Engl J Med. 2010;8:711–34. doi:10.1056/NEJMoa1003466
Parry RV, Chemnitz JM, Frauwirth KA et al. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms // Mol Cell Biol 2005;25(21):9543–53. doi:10.1128/MCB.25.21.9543-9553.2005
Freeman GJ, Long AJ, Iwai Y et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation // J Exp Med. 2000;192(7):1027–34. doi:10.1084/jem.192.7.1027
Dong H, Strome SE, Salomao DR et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion // Nat Med. 2002;8(8):793–800. doi:10.1038/nm730
Topalian SL, Drake CG, Pardoll DM. Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity // Curr Opin Immunol. 2012;24(2):207–12. doi:10.1016/j.coi.2011.12.009
Socinski MA, Bondarenko I, Karaseva NA et al. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced nonsmall-cell lung cancer: final results of a phase III trial // J Clin Oncol. 2012;30:2055–62. doi:10.1200/JCO.2011.39.5848
Brahmer J, Reckamp KL, Baas P et al. Nivolumab versus docetaxel in advanced squamous-cell nonsmall-cell lung cancer // N Engl J Med. 2015;373:1627–39. doi:10.1056/NEJMoa1507643
Borghaei H, Paz-Ares L, Horn L et al. Nivolumab versus docetaxel in advanced nonsquamous nonsmall-cell lung cancer // N Engl J Med. 2015;373:123–35. doi:10.1056/NEJMoa1507643
Herbst RS, Baas P, Kim DW et al. Pembrolizumab versus docetaxel for previously treated PD-L1- positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial // Lancet. 2016;387:1540–50. doi:10.1016/S0140-6736(15)01281-7
Fehrenbacher L, Spira A, Ballinger M et al. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial // Lancet. 2016;387:1837–46. doi:10.1016/S0140-6736(16)00587-0
Rittmeyer A, Barlesi F, Waterkamp D et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicenter randomised controlled trial // Lancet. 2017;389:255–65. doi:10.1016/S0140-6736(16)32517-X
Reck M, Rodriquez-Abreu D, Robinson AG et al. Pembrolizumab versus chemotherapy for PD-L1 positive non-small-cell lung cancer // N Engl J Med. 2016;375:1823–33. doi:10.1056/NEJMoa1606774
Gandhi L, Rodrigues-Abreu D, Gadgeel S et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer // N Engl J Med. 2018;378:2078–92. doi:10.1056/NEJMoa1801005
Langer CJ, Gadgeel SM, Borghaei H et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study // Lancet Oncol. 2016;17:1497–508. doi:10.1016/S1470-2045(16)30498-3
Socinski MA, Jotte RM, Cappuzzo F et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC // N Engl J Med. 2018;378:2280–301. doi:10.1056/NEJMoa1716948
Auperin A, Le Pechoux C, Rolland E et al. Metaanalysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer // J Clin Oncol. 2010;28:2181–90. doi:10.1200/JCO.2009.26.2543
Antonia SJ, Villegas A, Daniel D et al. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer // N Engl J Med. 2017;377:1919–29. doi:10.1056/NEJMoa1709937
Owen D, Chaft J. Immunotherapy in surgically resectable non-small-cell lung cancer // J Thorac Dis. 2018;10(suppl. 3):S404–11. doi:10.21037/jtd.2017.12.93
Liu J, Blake SJ, Yong MC et al. Improved efficacy of neoadjuvant compared to adjuvant immunotherapy to eradicate metastatic disease // Cancer Discov. 2016;6:1382–99. doi:10.1158/2159-8290.CD-16-0577
Rozeman EA, Blank CU, VanAkkooi A et al. Neoadjuvant ipilimumab 1 nivolumab (IPI 1 NIVO) in palpable stage III melanoma: updated data from the OpACIN trial and first immunological analyses // J Clin Oncol. 2017;35(suppl. 15):9586. doi:10.1056/NEJMoa1910231
Schmid P, Park YH, Munoz-Couselo E et al. Pembrolizumab (pembro) 1 chemotherapy (chemo) as neoadjuvant treatment for triple negative breast cancer (TNBC): preliminary results fromKEYNOTE173 // J ClinOncol. 2017;35:556. doi:10.1200/JCO.2017.35.15suppl.556
Carthon BC, Wolchok JD, Yuan J et al. Preoperative CTLA-4 blockade: tolerability and immune monitoring in the setting of a presurgical clinical trial // Clin Cancer Res. 2010;16:2861–71. doi:10.1158/1078-0432.CCR-10-0569
Forde PM, Chaft JE, William WN et al. Neoadjuvant PD-1 blockade in reseсtable lung cancer // N Engl J Med. 2018;378:1976–86. doi:10.1056/NEJMoa1716078
Bott MJ, Yang SC, Park BJ et al. Initial results of pulmonary resection after neoadjuvant nivolumab in patients with resectable non-small cell lung cancer // J Thorac Cardiovasc Surg. 2019;158:269–76. doi:10.1016/j.jtcvs.2018.11.124
Rusch V, Chaft JE, Johnson B et al. Neoadjuvant atezolizumab in respectable non-small-cell lung cancer (NSCLC): initial results from a multicenter study (LCMC3). Abstr. presented at American Society of Clinical Oncology Annual Meeting. Chicago, IL, June 3, 2018 // Journal of Clinical Oncology. 2018;36(suppl. 15):8541–8541. doi:10.1200/JCO.2018.36.15_suppl.8541
Provencio-Pulla M, Nadal-Alforja E, Cobo M et al. Neoadjuvant chemotherapy and nivolumab in resectable non-small-cell lung cancer (NADIM): an open-label, multicentre, single-arm, phase 2 trial // Lancet Oncol. 2020;21(11):1413–1422. doi:10.1016/S1470-2045(20)30453-8
Cascone T, William WN, Weissferdt A et al. Neoadjuvant nivolumab (N) or nivolumab plus ipilimumab (NI) for resectable non-small cell lung cancer (NSCLC): clinical results from the NEOSTAR study // J Clin Oncol. 2019;37(15_suppl):8504 [abstract]. doi:10.1038/s41591-020-01224-2
Hellmann MD, Chaft JE, William WN et al. Pathological response after neoadjuvant chemotherapy in resectable non-small-cell lung cancers: proposal for the use of major pathological response as a surrogate endpoint // Lancet Oncol. 2014;15:e42–50. doi:10.1016/S1470-2045(13)70334-6
Hellman MD, Ciuleanu TE, Pluzanski A et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden // N Engl J Med. 2018;378:2093–104. doi:10.1056/NEJMoa1801946
Eggermont AM, Chiarion-Sileni V, Grob JJ et al. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial // Lancet Oncol. 2015;16:522–30. doi:10.1016/S1470-2045(15)70271-8
Weber J, Mandala M, Del Vecchio M et al. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma // N Engl J Med. 2017;377:1824–35. doi:10.1056/NEJMoa1709030
Vansteenkiste J, Wauters E, Reymen B et al. Current status of immune checkpoint inhibition in early-stage NSCLC // Ann Oncol. 2019;30(8):1244-1253. doi:10.1093/annonc/mdz175
Bakos O, Lawson C, Rouleau S et al. Combining surgery and immuno-therapy: turning an immunosuppressive effect into a therapeutic oppor-tunity // J Immunother Cancer. 2018;6:86.
Patel SA, Minn AJ. Combination cancer therapy with immune check-point blockade: mechanisms and strategies // Immunity. 2018;48(3):417–433.
Broderick S. R. Adjuvant and Neoadjuvant Immunotherapy in Non-small Cell Lung // Cancer Thorac Surg Clin. 2020;30:215–220. doi:org/10.1016/j.thorsurg.2020.01.001
Shaverdian N, Lisberg AE, Bornazyan K et al. Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial // Lancet Oncol. 2017;18(7):895–903. doi:10.1016/S1470-2045(17)30380-7
Рагулин Ю.А. Сочетание иммунотерапии и лучевой терапии при немелкоклеточном раке легкого // Онкология. 2018;7(5):90–96 doi:10.17116/onkolog2018705190 [ Ragulin YuA. The combination of immunotherapy and radiation therapy for non-small cell lung cancer // Oncologiya. 2018;7(5):90–96 (In Russ.)]. doi:10.17116/onkolog2018705190
Yang H, Jin T, Li M et al. Synergistic effect of immunotherapy and radiotherapy in non-small cell lung cancer: current clinical trials and prospective challenges // Precision Clinical Medicine. 2019:1–14. doi:10.1093/pcmedi/pbz004
Altorki NK, Borczuk AC, Saxena A et al. P2.04-92 Neoadjuvant Durvalumab with or Without Sub-Ablative Stereotactic Radiotherapy (SBRT) in Patients with Resectable NSCLC (NCT02904954) // J. of Thorac. Oncol. 2019;14(10):S746. doi:10.1016/j.jtho.2019.08.1597
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
© АННМО «Вопросы онкологии», Copyright (c) 2022