nach oben

Clinical and Translational Oncology

Erschienen in:

12.01.2019 | Review Article

The role of immunotherapy in small cell lung cancer

verfasst von: A. Calles, G. Aguado, C. Sandoval, R. Álvarez

Erschienen in: Clinical and Translational Oncology | Ausgabe 8/2019

Einloggen, um Zugang zu erhalten

Abstract

Despite decades of research, prognosis for SCLC patients remains poor, and treatment options limited. SCLC is an immunogenic tumor with high somatic mutation rates due to tobacco exposure resulting in potential neo-antigens, the presence of suppressed immune responses, and occurrence of paraneoplastic disorders. The use of T cell immune-checkpoint inhibitors (anti-PD1: nivolumab, pembrolizumab; anti-PD-L1: atezolizumab, durvalumab; anti-CTLA-4: ipilimumab, tremelimumab) have shown promising antitumor activity with the potential to prolong survival in SCLC patients. In fact, atezolizumab when combined with chemotherapy has achieved the milestone of being the first drug to improve survival in patients with newly diagnosed extensive-stage SCLC. Other immunotherapeutic approaches evaluated in clinical trials for SCLC include the use of cytokines, cancer vaccines, antiganglioside therapies, TLR9 inhibition, anti-Notch signaling, and anti-CD47. This review discusses the rationale and clinical evidence of immunotherapy in SCLC, the conflictive clinical results of novel immunotherapeutic agents and combinatorial therapies under evaluation in SCLC patients.

Alvarado-Luna G, Morales-Espinosa D. Treatment for small cell lung cancer, where are we now?—a review. Transl Lung Cancer Res. 2016;5(1):26–38.PubMedPubMedCentral

George J, Lim JS, Jang SJ, Cun Y, Ozretic L, Kong G, et al. Comprehensive genomic profiles of small cell lung cancer. Nature. 2015;524(7563):47–53. https://doi.org/10.1038/nature14664.CrossRefPubMedPubMedCentral

Rudin CM, Ismaila N, Hann CL, Malhotra N, Movsas B, Norris K, et al. Treatment of small-cell lung cancer: American society of clinical oncology endorsement of the American college of chest physicians guideline. J Clin Oncol. 2015;33(34):4106–11. https://doi.org/10.1200/jco.2015.63.7918.CrossRefPubMed

Früh M, De Ruysscher D, Popat S, Crinò L, Peters S, Felip E, et al. Small-cell lung cancer (SCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(suppl_6):99–105. https://doi.org/10.1093/annonc/mdt178.CrossRef

Artal Cortés Á, Dómine Gómez M, Font Pous A, García Campelo R, Cobo Dolls M, Isla Casado D. SEOM clinical guidelines for the treatment of small-cell lung cancer. Clin Transl Oncol. 2010;12(1):27–31. https://doi.org/10.1007/s12094-010-0463-2.CrossRefPubMed

Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1–10. https://doi.org/10.1016/j.immuni.2013.07.012.CrossRefPubMed

Darnell RB. Onconeural antigens and the paraneoplastic neurologic disorders: at the intersection of cancer, immunity, and the brain. Proc Natl Acad Sci USA. 1996;93(10):4529–36.CrossRefPubMedPubMedCentral

Maddison P, Newsom-Davis J, Mills KR, Souhami RL. Favourable prognosis in Lambert-Eaton myasthenic syndrome and small-cell lung carcinoma. Lancet. 1999;353(9147):117–8. https://doi.org/10.1016/S0140-6736(05)76153-5.CrossRefPubMed

Spigel DR, Socinski MA. Rationale for chemotherapy, immunotherapy, and checkpoint blockade in SCLC: beyond traditional treatment approaches. J Thorac Oncol. 2013;8(5):587–98. https://doi.org/10.1097/JTO.0b013e318286cf88.CrossRefPubMed

10.

Wang W, Hodkinson P, McLaren F, Mackean MJ, Williams L, Howie SEM, et al. Histologic assessment of tumor-associated CD45(+) cell numbers is an independent predictor of prognosis in small cell lung cancer. Chest. 2013;143(1):146–51. https://doi.org/10.1378/chest.12-0681.CrossRefPubMed

11.

Koyama K, Kagamu H, Miura S, Hiura T, Miyabayashi T, Itoh R, et al. Reciprocal CD41 T-cell balance of effector CD62Llow CD41 and CD62LhighCD251 CD41 regulatory T cells in small cell lung cancer reflects disease stage. Clin Cancer Res. 2008;14(21):6770–9. https://doi.org/10.1158/1078-0432.Ccr-08-1156.CrossRefPubMed

12.

Ishii H, Azuma K, Kawahara A, Yamada K, Imamura Y, Tokito T, et al. Significance of programmed cell death-ligand 1 expression and its association with survival in patients with small cell lung cancer. J Thorac Oncol. 2015;10(3):426–30. https://doi.org/10.1097/JTO.0000000000000414.CrossRefPubMed

13.

Peifer M, Fernández-Cuesta L, Sos ML, George J, Seidel D, Kasper LH et al. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat Genet. 2012;44:1104. https://doi.org/10.1038/ng.2396. https://www.nature.com/articles/ng.2396#supplementary-information.

14.

Weiss GJ, Byron SA, Aldrich J, Sangal A, Barilla H, Kiefer JA, et al. A prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer progressing after first-line therapy. PLoS One. 2017;12(6):e0179170. https://doi.org/10.1371/journal.pone.0179170.CrossRefPubMedPubMedCentral

15.

Hellmann MD, Callahan MK, Awad MM, Calvo E, Ascierto PA, Atmaca A, et al. Tumor mutational burden and efficacy of nivolumab monotherapy and in combination with ipilimumab in small-cell lung cancer. Cancer Cell. 2018;33(5):853. https://doi.org/10.1016/j.ccell.2018.04.001.CrossRefPubMedPubMedCentral

16.

Gazdar AF, Bunn PA, Minna JD. Small-cell lung cancer: what we know, what we need to know and the path forward. Nat Rev Cancer. 2017;17:725. https://doi.org/10.1038/nrc.2017.87. https://www.nature.com/articles/nrc.2017.87#supplementary-information.

17.

Sabari JK, Lok BH, Laird JH, Poirier JT, Rudin CM. Unravelling the biology of SCLC: implications for therapy. Nat Rev Clin Oncol. 2017;14:549. https://doi.org/10.1038/nrclinonc.2017.71.CrossRefPubMedPubMedCentral

18.

Yarchoan M, Johnson III BA, Lutz ER, Laheru DA, Jaffee EM. Targeting neoantigens to augment antitumour immunity. Nat Rev Cancer. 2017;17:209. https://doi.org/10.1038/nrc.2016.154.CrossRefPubMedPubMedCentral

19.

Efremova M, Finotello F, Rieder D, Trajanoski Z. Neoantigens generated by individual mutations and their role in cancer immunity and immunotherapy. Front Immunol. 2017. https://doi.org/10.3389/fimmu.2017.01679.CrossRefPubMedPubMedCentral

20.

Dudley JC, Lin MT, Le DT, Eshleman JR. Microsatellite Instability as a Biomarker for PD-1 Blockade. Clin Cancer Res. 2016;22(4):813–20. https://doi.org/10.1158/1078-0432.Ccr-15-1678.CrossRefPubMed

21.

Goodman AM, Kato S, Bazhenova L, Patel SP, Frampton GM, Miller V, et al. Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers. Mol Cancer Ther. 2017;16(11):2598–608. https://doi.org/10.1158/1535-7163.Mct-17-0386.CrossRefPubMedPubMedCentral

22.

Doyle A, Martin WJ, Funa K, Gazdar A, Carney D, Martin SE, et al. Markedly decreased expression of class I histocompatibility antigens, protein, and mRNA in human small-cell lung cancer. J Exp Med. 1985;161(5):1135–51.CrossRefPubMed

23.

He Y, Rozeboom L, Rivard CJ, Ellison K, Dziadziuszko R, Yu H, et al. MHC class II expression in lung cancer. Lung Cancer. 2017;112:75–80. https://doi.org/10.1016/j.lungcan.2017.07.030.CrossRefPubMed

24.

Schalper KA, Carvajal-Hausdorf DE, McLaughlin JF, Altan M, Chiang AC, Velcheti V et al. Objective measurement and significance of PD-L1, B7-H3, B7-H4 and TILs in small cell lung cancer (SCLC). J Clin Oncol. 2016;34(15_suppl):8566. https://doi.org/10.1200/jco.2016.34.15_suppl.8566.CrossRef

25.

Antonia SJ, Mirza N, Fricke I, Chiappori A, Thompson P, Williams N, et al. Combination of p53 cancer vaccine with chemotherapy in patients with extensive stage small cell lung cancer. Clin Cancer Res. 2006;12(3 Pt 1):878–87. https://doi.org/10.1158/1078-0432.CCR-05-2013.CrossRefPubMed

26.

Rivalland G, Walkiewicz M, Wright GM, John T. Small cell lung cancer: the immune microenvironment and prognostic impact of checkpoint expression. J Clin Oncol. 2017;35(15_suppl):8569. https://doi.org/10.1200/jco.2017.35.15_suppl.8569.CrossRef

27.

Clamon G, Herndon J, Perry MC, Ozer H, Kreisman H, Maher T, et al. Interleukin-2 activity in patients with extensive small-cell lung cancer: a phase II trial of Cancer and Leukemia Group B. J Natl Cancer Inst. 1993;85(4):316–20.CrossRefPubMed

28.

Clamon G, Herndon J, Akerley W, Green M. Subcutaneous interleukin-2 as initial therapy for patients with extensive small cell lung cancer. Lung Cancer. 1998;19(1):25–9. https://doi.org/10.1016/S0169-5002(97)00070-6.CrossRefPubMed

29.

Zarogoulidis K, Ziogas E, Papagiannis A, Charitopoulos K, Dimitriadis K, Economides D, et al. Interferon alpha-2a and combined chemotherapy as first line treatment in SCLC patients: a randomized trial. Lung Cancer. 1996;15(2):197–205.CrossRefPubMed

30.

Zarogoulidis K, Ziogas E, Boutsikou E, Zarogoulidis P, Darwiche K, Kontakiotis T, et al. Immunomodifiers in combination with conventional chemotherapy in small cell lung cancer: a phase II, randomized study. Drug Des, Dev Ther. 2013;7:611–7. https://doi.org/10.2147/dddt.S43184.CrossRef

31.

Mattson K, Niiranen A, Pyrhonen S, Holsti LR, Holsti P, Kumpulainen E, et al. Natural interferon alfa as maintenance therapy for small cell lung cancer. Eur J Cancer. 1992;28a(8–9):1387–91.CrossRefPubMed

32.

Jett JR, Maksymiuk AW, Su JQ, Mailliard JA, Krook JE, Tschetter LK, et al. Phase III trial of recombinant interferon gamma in complete responders with small-cell lung cancer. J Clin Oncol. 1994;12(11):2321–6. https://doi.org/10.1200/jco.1994.12.11.2321.CrossRefPubMed

33.

Kelly K, Crowley JJ, Bunn PA Jr, Hazuka MB, Beasley K, Upchurch C, et al. Role of recombinant interferon alfa-2a maintenance in patients with limited-stage small-cell lung cancer responding to concurrent chemoradiation: a Southwest Oncology Group study. J Clin Oncol. 1995;13(12):2924–30. https://doi.org/10.1200/jco.1995.13.12.2924.CrossRefPubMed

34.

van Zandwijk N, Groen HJ, Postmus PE, Burghouts JT, ten Velde GP, Ardizzoni A, et al. Role of recombinant interferon-gamma maintenance in responding patients with small cell lung cancer. A randomised phase III study of the EORTC Lung Cancer Cooperative Group. Eur J Cancer. 1997;33(11):1759–66.CrossRefPubMed

35.

Pillai RN, Aisner J, Dahlberg SE, Rogers JS, DiPaola RS, Aisner S, et al. Interferon alpha plus 13-cis-retinoic acid modulation of BCL-2 plus paclitaxel for recurrent small-cell lung cancer (SCLC): an Eastern Cooperative Oncology Group study (E6501). Cancer Chemother Pharmacol. 2014;74(1):177–83. https://doi.org/10.1007/s00280-014-2427-7.CrossRefPubMedPubMedCentral

36.

Shengle Z, Carlos C-C, Zhang S, Reuter VE, Sucharita A, Bradley HW, et al. Selection of tumor antigens as targets for immune attack using immunohistochemistry: I. Focus on gangliosides. Int J Cancer. 1997;73(1):42–9. https://doi.org/10.1002/(sici)1097-0215(19970926)73:1%3c42:aid-ijc8%3e3.0.co;2-1.CrossRef

37.

Krug LM, Ragupathi G, Hood C, Kris MG, Miller VA, Allen JR, et al. Vaccination of patients with small-cell lung cancer with synthetic fucosyl GM-1 conjugated to keyhole limpet hemocyanin. Clin Cancer Res. 2004;10(18 Pt 1):6094–100. https://doi.org/10.1158/1078-0432.CCR-04-0482.CrossRefPubMed

38.

Krug LM, Ragupathi G, Ng KK, Hood C, Jennings HJ, Guo Z, et al. Vaccination of small cell lung cancer patients with polysialic acid or N-propionylated polysialic acid conjugated to keyhole limpet hemocyanin. Clin Cancer Res. 2004;10(3):916–23.CrossRefPubMed

39.

Krug LM, Ragupathi G, Hood C, George C, Hong F, Shen R, et al. Immunization with N-propionyl polysialic acid-KLH conjugate in patients with small cell lung cancer is safe and induces IgM antibodies reactive with SCLC cells and bactericidal against group B meningococci. Cancer Immunol Immunother. 2012;61(1):9–18. https://doi.org/10.1007/s00262-011-1083-6.CrossRefPubMed

40.

Chada S, Mhashilkar A, Roth JA, Gabrilovich D. Development of vaccines against self-antigens: the p53 paradigm. Curr Opin Drug Discov Devel. 2003;6(2):169–73.PubMed

41.

Vierboom MP, Nijman HW, Offringa R, van der Voort EI, van Hall T, van den Broek L, et al. Tumor eradication by wild-type p53-specific cytotoxic T lymphocytes. J Exp Med. 1997;186(5):695–704.CrossRefPubMedPubMedCentral

42.

Zwaveling S, Vierboom MP, Ferreira Mota SC, Hendriks JA, Ooms ME, Sutmuller RP, et al. Antitumor efficacy of wild-type p53-specific CD4(+) T-helper cells. Cancer Res. 2002;62(21):6187–93.PubMed

43.

Chiappori AA, Soliman H, Janssen WE, Antonia SJ, Gabrilovich DI. INGN-225: a dendritic cell-based p53 vaccine (Ad.p53-DC) in small cell lung cancer: observed association between immune response and enhanced chemotherapy effect. Expert Opin Biol Ther. 2010;10(6):983–91. https://doi.org/10.1517/14712598.2010.484801.CrossRefPubMedPubMedCentral

44.

Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature. 2011;480(7378):480–9. https://doi.org/10.1038/nature10673.CrossRefPubMedPubMedCentral

45.

Chen L, Flies DB. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol. 2013;13(4):227–42. https://doi.org/10.1038/nri3405.CrossRefPubMedPubMedCentral

46.

Apetoh L, Ladoire S, Coukos G, Ghiringhelli F. Combining immunotherapy and anticancer agents: the right path to achieve cancer cure? Ann Oncol. 2015;26(9):1813–23. https://doi.org/10.1093/annonc/mdv209.CrossRefPubMed

47.

Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252. https://doi.org/10.1038/nrc3239.CrossRefPubMedPubMedCentral

48.

Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677–704. https://doi.org/10.1146/annurev.immunol.26.021607.090331.CrossRefPubMed

49.

Reck M, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, et al. Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol. 2013;24(1):75–83. https://doi.org/10.1093/annonc/mds213.CrossRefPubMed

50.

Arriola E, Wheater M, Galea I, Cross N, Maishman T, Hamid D, et al. Outcome and biomarker analysis from a multicenter phase 2 study of ipilimumab in combination with carboplatin and etoposide as first-line therapy for extensive-stage SCLC. J Thorac Oncol. 2016;11(9):1511–21. https://doi.org/10.1016/j.jtho.2016.05.028.CrossRefPubMedPubMedCentral

51.

Reck M, Luft A, Szczesna A, Havel L, Kim SW, Akerley W, et al. Phase III randomized trial of ipilimumab plus etoposide and platinum versus placebo plus etoposide and platinum in extensive-stage small-cell lung cancer. J Clin Oncol. 2016;34(31):3740–8. https://doi.org/10.1200/JCO.2016.67.6601.CrossRefPubMed

52.

Antonia SJ, Lopez-Martin JA, Bendell J, Ott PA, Taylor M, Eder JP, 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(7):883–95. https://doi.org/10.1016/s1470-2045(16)30098-5.CrossRefPubMed

53.

Hellmann MD, Ott PA, Zugazagoitia J, Ready NE, Hann CL, De Braud FG, et al. Nivolumab (nivo) ± ipilimumab (ipi) in advanced small-cell lung cancer (SCLC): first report of a randomized expansion cohort from CheckMate 032. J Clin Oncol. 2017;35(15_suppl):8503. https://doi.org/10.1200/jco.2017.35.15_suppl.8503.CrossRef

54.

National Comprehensive Cancer Network. Small Cell Lung Cancer (Version 2.2018). https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. Accessed 15 Jun 2018.

55.

Horn L, Reck M, Gettinger SN, Spigel DR, Antonia SJ, Rupnow BA, et al. CheckMate 331: An open-label, randomized phase III trial of nivolumab versus chemotherapy in patients (pts) with relapsed small cell lung cancer (SCLC) after first-line platinum-based chemotherapy (PT-DC). J Clin Oncol. 2016;34(15_suppl):TPS8578. https://doi.org/10.1200/jco.2016.34.15_suppl.tps8578.CrossRef

56.

Ready N, Owonikoko TK, Postmus PE, Reck M, Peters S, Pieters A, et al. CheckMate 451: A randomized, double-blind, phase III trial of nivolumab (nivo), nivo plus ipilimumab (ipi), or placebo as maintenance therapy in patients (pts) with extensive-stage disease small cell lung cancer (ED-SCLC) after first-line platinum-based doublet chemotherapy (PT-DC). J Clin Oncol. 2016;34(15_suppl):TPS8579. https://doi.org/10.1200/jco.2016.34.15_suppl.tps8579.CrossRef

57.

De Ruysscher D, Pujol JL, Popat S, Reck M, Le Pechoux C, Liston A, et al. STIMULI: a randomised open-label phase II trial of consolidation with nivolumab and ipilimumab in limited-stage SCLC after standard of care chemo-radiotherapy conducted by ETOP and IFCT. Ann Oncol. 2016;27(suppl_6):1430TiP-TiP. https://doi.org/10.1093/annonc/mdw389.08.CrossRef

58.

Ott PA, Elez E, Hiret S, Kim DW, Morosky A, Saraf 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(34):3823–9. https://doi.org/10.1200/JCO.2017.72.5069.CrossRefPubMed

59.

Chung HC, Lopez-Martin JA, Kao SC-H, Miller WH, Ros W, Gao B et al. Phase 2 study of pembrolizumab in advanced small-cell lung cancer (SCLC): KEYNOTE-158. J Clin Oncol. 2018;36(15_suppl):8506-. https://doi.org/10.1200/jco.2018.36.15_suppl.8506.

60.

Gadgeel SM, Pennell NA, Fidler MJ, Halmos B, Bonomi P, Stevenson J, et al. Phase II study of maintenance pembrolizumab in patients with extensive-stage small cell lung cancer (SCLC). J Thorac Oncol. 2018. https://doi.org/10.1016/j.jtho.2018.05.002.CrossRefPubMedPubMedCentral

61.

Rudin CM, Shen L, Pietanza MC. KEYNOTE-604: Phase 3 trial of pembrolizumab plus etoposide/platinum (EP) for first-line treatment of extensive stage small-cell lung cancer (ES-SCLC). Ann Oncol. 2017;28(suppl_5):mdx386.008. https://doi.org/10.1093/annonc/mdx386.008.CrossRef

62.

Sequist LV, Chiang A, Gilbert J, Gordon M, Conkling PR, Thompson D, et al. Clinical activity, safety and predictive biomarkers results from a phase Ia atezolizumab (atezo) trial in extensive-stage small cell lung cancer (ES-SCLC). Ann Oncol. 2016;27(suppl_6):1425PD-PD. https://doi.org/10.1093/annonc/mdw389.03.CrossRef

63.

Pujol JL, Greillier L, Audigier Valette C, Moro-Sibilot D, Uwer L, Hureaux J, et al. A randomized non-comparative phase II study of anti–PD-L1 atezolizumab or chemotherapy as second-line therapy in patients with small cell lung cancer: results from the IFCT-1603 trial. Ann Oncol. 2018;29(Suppl 8):1664O. https://doi.org/10.1093/annonc/mdy298.CrossRef

64.

Horn L, Reck M, Mok TSK, Johnson M, Waterkamp D, Lam S, et al. A Phase III study of atezolizumab with carboplatin plus etoposide in patients with extensive-stage small cell lung cancer (IMpower133). Ann Oncol. 2016;27(suppl_6):1431TiP-TiP. https://doi.org/10.1093/annonc/mdw389.09.CrossRef

65.

Horn L, Mansfield AS, Szczęsna A, Havel L, Krzakowski M, Hochmair MJ et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018;379:2220–9. https://doi.org/10.1056/nejmoa1809064.CrossRefPubMed

66.

Pawel JV, Vynnychenko I, Jiang H, Huang Y, Dennis PA. A phase II, open-label, multi-arm study of novel combinations of immunotherapies or DDR inhibitors in platinum-refractory, extensive disease small-cell lung cancer (ED-SCLC): BALTIC. J Clin Oncol. 2017;35(15_suppl):TPS8585-TPS. https://doi.org/10.1200/jco.2017.35.15_suppl.tps8585.CrossRef

67.

Paz-Ares L, Jiang H, Huang Y, Dennis P. CASPIAN: phase 3 study of first-line durvalumab ± tremelimumab + platinum-based chemotherapy vs chemotherapy alone in ED-SCLC. J Thorac Oncol. 2017;12(11):S2398. https://doi.org/10.1016/j.jtho.2017.11.015.CrossRef

68.

Jiao S, Xia W, Yamaguchi H, Wei Y, Chen MK, Hsu JM, et al. PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression. Clin Cancer Res. 2017;23(14):3711–20. https://doi.org/10.1158/1078-0432.CCR-16-3215.CrossRefPubMedPubMedCentral

69.

Krebs M, Ross K, Kim S, De Jonge M, Barlesi F, Postel-Vinay S, et al. An open-label, multitumor phase II basket study of olaparib and durvalumab (MEDIOLA): results in patients with relapsed SCLC. J Thorac Oncol. 2017;12(11):S2044–S5. https://doi.org/10.1016/j.jtho.2017.09.1040.CrossRef

70.

Schmidt M, Hagner N, Marco A, Konig-Merediz SA, Schroff M, Wittig B. Design and structural requirements of the potent and safe TLR-9 agonistic immunomodulator MGN1703. Nucleic Acid Ther. 2015;25(3):130–40. https://doi.org/10.1089/nat.2015.0533.CrossRefPubMedPubMedCentral

71.

Thomas M, Ponce-Aix S, Navarro Mendivil A, Riera Knorrenschild J, Schmidt M, Krikow M, et al. Top-line data from the randomized phase 2 IMPULSE study in small-cell lung cancer (SCLC): Immunotherapeutic maintenance treatment with lefitolimod. Ann Oncol. 2017;28(suppl_5):mdx386. https://doi.org/10.1093/annonc/mdx386.CrossRef

72.

Saunders LR, Bankovich AJ, Anderson WC, Aujay MA, Bheddah S, Black K, et al. A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo. Sci Transl Med. 2015;7(302):302ra136. https://doi.org/10.1126/scitranslmed.aac9459.CrossRefPubMedPubMedCentral

73.

Rudin CM, Pietanza MC, Bauer TM, Ready N, Morgensztern D, Glisson BS, et al. Rovalpituzumab tesirine, a DLL3-targeted antibody-drug conjugate, in recurrent small-cell lung cancer: a first-in-human, first-in-class, open-label, phase 1 study. Lancet Oncol. 2017;18(1):42–51. https://doi.org/10.1016/s1470-2045(16)30565-4.CrossRefPubMed

74.

Carbone DP, Morgensztern D, Moulec SL, Santana-Davila R, Ready N, Hann CL, et al. Efficacy and safety of rovalpituzumab tesirine in patients with DLL3-expressing, ≥ 3rd line small cell lung cancer: results from the phase 2 TRINITY study. J Clin Oncol. 2018;36(15_suppl):8507. https://doi.org/10.1200/jco.2018.36.15_suppl.8507.CrossRef

75.

Daniel DB, Rudin CM, Hart L, Spigel DR, Edelman MJ, Goldschmidt J, et al. Results of a randomized, placebo-controlled, phase 2 study of tarextumab (TRXT, anti-Notch2/3) in combination with etoposide and platinum (EP) in patients (pts) with untreated extensive-stage small-cell lung cancer (ED-SCLC). Ann Oncol. 2017;28(suppl_5):mdx386.004. https://doi.org/10.1093/annonc/mdx386.004.CrossRef

76.

Chu QSC, Markman B, Leighl N, Krug L, Rudin C, Lathers D, et al. A phase 1/2 trial of a monoclonal antibody targeting fucosyl GM1 in relapsed/refractory small cell lung cancer (SCLC): safety and preliminary efficacy. Ann Oncol. 2016;27(suppl_6):1427PD. https://doi.org/10.1093/annonc/mdw389.05.CrossRef

77.

Chu QSC, van Herpen C, Leighl NB, Markman B, Clarke S, Juergens RA, et al. Initial results of BMS-986012, a first-in-class fucosyl-GM1 mAb, in combination with nivolumab, in pts with relapsed/refractory (rel/ref) small-cell lung cancer (SCLC). Ann Oncol. 2017;28(suppl_5):mdx386.002. https://doi.org/10.1093/annonc/mdx386.002.CrossRef

78.

Mueller BM, Romerdahl CA, Gillies SD, Reisfeld RA. Enhancement of antibody-dependent cytotoxicity with a chimeric anti-GD2 antibody. J Immunol. 1990;144(4):1382–6.PubMed

79.

Navid F, Santana VM, Barfield RC. Anti-GD2 antibody therapy for GD2-expressing tumors. Curr Cancer Drug Targets. 2010;10(2):200–9.CrossRefPubMedPubMedCentral

80.

Dhillon S. Dinutuximab: first global approval. Drugs. 2015;75(8):923–7. https://doi.org/10.1007/s40265-015-0399-5.CrossRefPubMed

81.

Castel V, Segura V, Canete A. Treatment of high-risk neuroblastoma with anti-GD2 antibodies. Clin Transl Oncol. 2010;12(12):788–93. https://doi.org/10.1007/s12094-010-0600-y.CrossRefPubMed

82.

Weiskopf K. Cancer immunotherapy targeting the CD47/SIRPalpha axis. Eur J Cancer. 2017;76:100–9. https://doi.org/10.1016/j.ejca.2017.02.013.CrossRefPubMed

83.

Xiang Y-R, Liu L. Eating cancer cells by blocking CD47 signaling: cancer therapy by targeting the innate immune checkpoint. Cancer Transl Med. 2017;3(6):200–8. https://doi.org/10.4103/ctm.ctm_26_17.CrossRef

84.

Willingham SB, Volkmer JP, Gentles AJ, Sahoo D, Dalerba P, Mitra SS, et al. The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors. Proc Natl Acad Sci USA. 2012;109(17):6662–7. https://doi.org/10.1073/pnas.1121623109.CrossRefPubMedPubMedCentral

85.

Weiskopf K, Jahchan NS, Schnorr PJ, Cristea S, Ring AM, Maute RL, et al. CD47-blocking immunotherapies stimulate macrophage-mediated destruction of small-cell lung cancer. J Clin Invest. 2016;126(7):2610–20. https://doi.org/10.1172/JCI81603.CrossRefPubMedPubMedCentral

86.

Navarro A, Felip E. Pembrolizumab in advanced pretreated small cell lung cancer patients with PD-L1 expression: data from the KEYNOTE-028 trial: a reason for hope? Transl Lung Cancer Res. 2017;6(Suppl 1):S78–83. https://doi.org/10.21037/tlcr.2017.10.04.CrossRefPubMedPubMedCentral

87.

Giaccone G, Debruyne C, Felip E, Chapman PB, Grant SC, Millward M, et al. Phase III study of adjuvant vaccination with Bec2/bacille Calmette-Guerin in responding patients with limited-disease small-cell lung cancer (European Organisation for Research and Treatment of Cancer 08971-08971B; Silva Study). J Clin Oncol. 2005;23(28):6854–64. https://doi.org/10.1200/jco.2005.17.186.CrossRefPubMed

Titel: The role of immunotherapy in small cell lung cancer
verfasst von: A. Calles
G. Aguado
C. Sandoval
R. Álvarez
Publikationsdatum: 12.01.2019
Verlag: Springer International Publishing
Erschienen in: Clinical and Translational Oncology / Ausgabe 8/2019
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI: https://doi.org/10.1007/s12094-018-02011-9

Neu im Fachgebiet Onkologie

25.04.2024 | Nierenkarzinom | Nachrichten

Springer Medizin

The role of immunotherapy in small cell lung cancer

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 8/2019

Efficacy of nivolumab as checkpoint inhibitor drug on survival rate of patients with relapsed/refractory classical Hodgkin lymphoma: a meta-analysis of prospective clinical study

Clinical significance of serum EGFR gene mutation and serum tumor markers in predicting tyrosine kinase inhibitor efficacy in lung adenocarcinoma

Survival after biochemical failure in prostate cancer treated with radiotherapy: Spanish Registry of Prostate Cancer (RECAP) database outcomes

Neurotrophic tropomyosin receptor kinase (NTRK) and nerve growth factor (NGF) are not expressed in Caucasian patients with biliary tract cancers: pooled data from three independent cohorts

Critical evaluation of platelet size as a prognostic biomarker in colorectal cancer across multiple treatment settings: a retrospective cohort study

Letrozole improves the sensitivity of breast cancer cells overexpressing aromatase to cisplatin via down-regulation of FEN1

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie