799
Views
10
CrossRef citations to date
0
Altmetric
Review

Prospects of targeted and immune therapies in SCLC

, &
Pages 151-167 | Received 30 Jul 2018, Accepted 10 Dec 2018, Published online: 28 Dec 2018

References

  • Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86.
  • Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of disease study 2010. Lancet. 2012;380:2095–2128.
  • Torre LA, Siegel RL, Jemal A. Lung cancer statistics. Adv Exp Med Biol. 2016;893:1–19.
  • Torre LA, Siegel RL, Ward EM, et al. Global cancer incidence and mortality rates and trends–an update. Cancer Epidemiol Biomarkers Prev. 2016;25:16–27.
  • Ou SH, Ziogas A, Zell JA. Prognostic factors for survival in extensive stage small cell lung cancer (ED-SCLC): the importance of smoking history, socioeconomic and marital statuses, and ethnicity. J Thorac Oncol. 2009;4:37–43.
  • Pesch B, Kendzia B, Gustavsson P, et al. Cigarette smoking and lung cancer–relative risk estimates for the major histological types from a pooled analysis of case-control studies. Int J Cancer J Inter Du Cancer. 2012;131:1210–1219.
  • Huang R, Wei Y, Hung RJ, et al. Associated links among smoking, chronic obstructive pulmonary disease, and small cell lung cancer: a pooled analysis in the international lung cancer consortium. EBioMedicine. 2015;2:1677–1685.
  • Khuder SA, Mutgi AB. Effect of smoking cessation on major histologic types of lung cancer. Chest. 2001;120:1577–1583.
  • Team NLSTR, Aberle DR, Adams AM, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365:395–409.
  • Silva M, Galeone C, Sverzellati N, et al. Screening with low-dose computed tomography does not improve survival of small cell lung cancer. J Thorac Oncol. 2016;11:187–193.
  • Aberle DR, DeMello S, Berg CD, et al. Results of the two incidence screenings in the national lung screening trial. N Engl J Med. 2013;369:920–931.
  • Fruh M, De Ruysscher D, Popat S, et al. Small-cell lung cancer (SCLC): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann oncol. 2013;24(Suppl 6):vi99–105.
  • 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;30:1692–1698.
  • O’Brien ME, Ciuleanu TE, Tsekov H, et al. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol. 2006;24:5441–5447.
  • 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;25:2086–2092.
  • Smit EF, Fokkema E, Biesma B, et al. A phase II study of paclitaxel in heavily pretreated patients with small-cell lung cancer. Br J Cancer. 1998;77:347–351.
  • Yamamoto N, Tsurutani J, Yoshimura N, et al. Phase II study of weekly paclitaxel for relapsed and refractory small cell lung cancer. Anticancer Res. 2006;26:777–781.
  • Pietanza MC, Kadota K, Huberman K, et al. Phase II trial of temozolomide in patients with relapsed sensitive or refractory small cell lung cancer, with assessment of methylguanine-DNA methyltransferase as a potential biomarker. Clin Cancer Res. 2012;18:1138–1145.
  • Zauderer MG, Drilon A, Kadota K, et al. Trial of a 5-day dosing regimen of temozolomide in patients with relapsed small cell lung cancers with assessment of methylguanine-DNA methyltransferase. Lung Cancer. 2014;86:237–240.
  • von Pawel J, Jotte R, Spigel DR, et al. Randomized phase III trial of amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer. J Clin Oncol. 2014;32:4012–4019.
  • Bordi P, Tiseo M, Barbieri F, et al. Gene mutations in small-cell lung cancer (SCLC): results of a panel of 6 genes in a cohort of Italian patients. Lung Cancer. 2014;86:324–328.
  • Lou G, Yu X, Song Z. Molecular profiling and survival of completely resected primary pulmonary neuroendocrine carcinoma. Clin Lung Cancer. 2017;18:e197–e201.
  • Shibata T, Kokubu A, Tsuta K, et al. Oncogenic mutation of PIK3CA in small cell lung carcinoma: a potential therapeutic target pathway for chemotherapy-resistant lung cancer. Cancer Lett. 2009;283:203–211.
  • Schultheis AM, Bos M, Schmitz K, et al. Fibroblast growth factor receptor 1 (FGFR1) amplification is a potential therapeutic target in small-cell lung cancer. Mod Pathol. 2014;27:214–221.
  • Byers LA, Wang J, Nilsson MB, et al. Proteomic profiling identifies dysregulated pathways in small cell lung cancer and novel therapeutic targets including PARP1. Cancer Discov. 2012;2:798–811.
  • Boldrini L, Ursino S, Gisfredi S, et al. Expression and mutational status of c-kit in small-cell lung cancer: prognostic relevance. Clin Cancer Res. 2004;10:4101–4108.
  • Lawson MH, Cummings NM, Rassl DM, et al. Bcl-2 and beta1-integrin predict survival in a tissue microarray of small cell lung cancer. Br J Cancer. 2010;103:1710–1715.
  • Sharp A, Bhosle J, Abdelraouf F, et al. Development of molecularly targeted agents and immunotherapies in small cell lung cancer. Eur J Cancer. 2016;60:26–39.
  • George J, Lim JS, Jang SJ, et al. Comprehensive genomic profiles of small cell lung cancer. Nature. 2015;524:47–53.
  • Sabari JK, Lok BH, Laird JH, et al. Unravelling the biology of SCLC: implications for therapy. Nat Rev Clin Oncol. 2017;14:549–561.
  • Allison Stewart C, Tong P, Cardnell RJ, et al. Dynamic variations in epithelial-to-mesenchymal transition (EMT), ATM, and SLFN11 govern response to PARP inhibitors and cisplatin in small cell lung cancer. Oncotarget. 2017;8:28575–28587.
  • Peifer M, Fernandez-Cuesta L, Sos ML, et al. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat Genet. 2012;44:1104–1110.
  • Cardnell RJ, Feng Y, Mukherjee S, et al. Activation of the PI3K/mTOR pathway following PARP inhibition in small cell lung cancer. PLoS One. 2016;11:e0152584.
  • Hook KE, Garza SJ, Lira ME, et al. An integrated genomic approach to identify predictive biomarkers of response to the aurora kinase inhibitor PF-03814735. Mol Cancer Ther. 2012;11:710–719.
  • Sos ML, Dietlein F, Peifer M, et al. A framework for identification of actionable cancer genome dependencies in small cell lung cancer. Proc Natl Acad Sci USA. 2012;109:17034–17039.
  • Bruzzese F, Rocco M, Castelli S, et al. Synergistic antitumor effect between vorinostat and topotecan in small cell lung cancer cells is mediated by generation of reactive oxygen species and DNA damage-induced apoptosis. Mol Cancer Ther. 2009;8:3075–3087.
  • Palma JP, Wang YC, Rodriguez LE, et al. ABT-888 confers broad in vivo activity in combination with temozolomide in diverse tumors. Clin Cancer Res. 2009;15:7277–7290.
  • Camirand A, Pollak M. Co-targeting IGF-1R and c-kit: synergistic inhibition of proliferation and induction of apoptosis in H 209 small cell lung cancer cells. Br J Cancer. 2004;90:1825–1829.
  • Lochmann TL, Floros KV, Naseri M, et al. Venetoclax is effective in small-cell lung cancers with high BCL-2 expression. Clin Cancer Res. 2018;24:360–369.
  • Polley E, Kunkel M, Evans D, et al. Small cell lung cancer screen of oncology drugs, investigational agents, and gene and microRNA expression. J Natl Cancer Inst. 2016;108: djw122.
  • Rudin CM, Durinck S, Stawiski EW, et al. Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer. Nat Genet. 2012;44:1111–1116.
  • Takebe N, Nguyen D, Yang SX. Targeting notch signaling pathway in cancer: clinical development advances and challenges. Pharmacol Ther. 2014;141:140–149.
  • Kunnimalaiyaan M, Chen H. Tumor suppressor role of Notch-1 signaling in neuroendocrine tumors. Oncologist. 2007;12:535–542.
  • Borromeo MD, Savage TK, Kollipara RK, et al. ASCL1 and NEUROD1 reveal heterogeneity in pulmonary neuroendocrine tumors and regulate distinct genetic programs. Cell Rep. 2016;16:1259–1272.
  • Henke RM, Meredith DM, Borromeo MD, et al. Ascl1 and Neurog2 form novel complexes and regulate Delta-like3 (Dll3) expression in the neural tube. Dev Biol. 2009;328:529–540.
  • Semenova EA, Nagel R, Berns A. Origins, genetic landscape, and emerging therapies of small cell lung cancer. Genes Dev. 2015;29:1447–1462.
  • Saunders LR, Bankovich AJ, Anderson WC, et al. A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo. Sci Transl Med. 2015;7:302ra136.
  • Gazdar AF, Carney DN, Nau MM, et al. Characterization of variant subclasses of cell lines derived from small cell lung cancer having distinctive biochemical, morphological, and growth properties. Cancer Res. 1985;45:2924–2930.
  • Carney DN, Gazdar AF, Bepler G, et al. Establishment and identification of small cell lung cancer cell lines having classic and variant features. Cancer Res. 1985;45:2913–2923.
  • George J, Walter V, Peifer M, et al. Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors. Nat Commun. 2018;9:1048.
  • Dowlati A, Lipka MB, McColl K, et al. Clinical correlation of extensive-stage small-cell lung cancer genomics. Ann oncol. 2016;27:642–647.
  • Indovina P, Pentimalli F, Casini N, et al. RB1 dual role in proliferation and apoptosis: cell fate control and implications for cancer therapy. Oncotarget. 2015;6:17873–17890.
  • Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70.
  • Tanno S, Ohsaki Y, Nakanishi K, et al. Human small cell lung cancer cells express functional VEGF receptors, VEGFR-2 and VEGFR-3. Lung Cancer. 2004;46:11–19.
  • Lucchi M, Mussi A, Fontanini G, et al. Small cell lung carcinoma (SCLC): the angiogenic phenomenon. Eur J Cardio-Thorac Surg. 2002;21:1105–1110.
  • Nowak K, Rafat N, Belle S, et al. Circulating endothelial progenitor cells are increased in human lung cancer and correlate with stage of disease. Eur J Cardio-Thorac Surg. 2010;37:758–763.
  • Canadas I, Taus A, Villanueva X, et al. Angiopoietin-2 is a negative prognostic marker in small cell lung cancer. Lung Cancer. 2015;90:302–306.
  • Salven P, Ruotsalainen T, Mattson K, et al. High pre-treatment serum level of vascular endothelial growth factor (VEGF) is associated with poor outcome in small-cell lung cancer. Int J Cancer. 1998;79:144–146.
  • Hasegawa Y, Takanashi S, Okudera K, et al. Vascular endothelial growth factor level as a prognostic determinant of small cell lung cancer in Japanese patients. Intern Med. 2005;44:26–34.
  • Mullen PJ, Yu R, Longo J, et al. The interplay between cell signalling and the mevalonate pathway in cancer. Nat Rev Cancer. 2016;16:718–731.
  • Khanzada UK, Pardo OE, Meier C, et al. Potent inhibition of small-cell lung cancer cell growth by simvastatin reveals selective functions of Ras isoforms in growth factor signalling. Oncogene. 2006;25:877–887.
  • Michael M, Babic B, Khokha R, et al. Expression and prognostic significance of metalloproteinases and their tissue inhibitors in patients with small-cell lung cancer. J Clin Oncol. 1999;17:1802–1808.
  • Brown PD, Giavazzi R. Matrix metalloproteinase inhibition: a review of anti-tumour activity. Ann Oncol. 1995;6:967–974.
  • Brown PD. Matrix metalloproteinase inhibitors: a novel class of anticancer agents. Adv Enzyme Regul. 1995;35:293–301.
  • Goldenberg DM, Cardillo TM, Govindan SV, et al. Trop-2 is a novel target for solid cancer therapy with sacituzumab govitecan (IMMU-132), an antibody-drug conjugate (ADC). Oncotarget. 2015;6:22496–22512.
  • Lee SM, Woll PJ, Rudd R, et al. Anti-angiogenic therapy using thalidomide combined with chemotherapy in small cell lung cancer: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst. 2009;101:1049–1057.
  • Arnold AM, Seymour L, Smylie M, et al. Phase II study of vandetanib or placebo in small-cell lung cancer patients after complete or partial response to induction chemotherapy with or without radiation therapy: national cancer institute of canada clinical trials group study BR.20. J Clin Oncol. 2007;25:4278–4284.
  • Seckl MJ, Ottensmeier CH, Cullen M, et al. Multicenter, phase III, randomized, double-blind, placebo-controlled trial of pravastatin added to first-line standard chemotherapy in small-cell lung cancer (LUNGSTAR). J Clin Oncol. 2017;35:1506–1514.
  • Shepherd FA, Giaccone G, Seymour L, et al. Prospective, randomized, double-blind, placebo-controlled trial of marimastat after response to first-line chemotherapy in patients with small-cell lung cancer: a trial of the national cancer institute of canada-clinical trials group and the european organization for research and treatment of cancer. J Clin Oncol. 2002;20:4434–4439.
  • Baize N, Monnet I, Greillier L, et al. Second-line treatments of small-cell lung cancers. Expert Rev Anticancer Ther. 2017;17:1033–1043.
  • Tentori L, Graziani G. Chemopotentiation by PARP inhibitors in cancer therapy. Pharmacol Res. 2005;52:25–33.
  • Pietanza MC, Waqar SN, Krug LM, et al. Randomized, double-blind, phase ii study of temozolomide in combination with either veliparib or placebo in patients with relapsed-sensitive or refractory small-cell lung cancer. J Clin Oncol. 2018;36(23):2386 2304.
  • Tarhini A, Kotsakis A, Gooding W, et al. Phase II study of everolimus (RAD001) in previously treated small cell lung cancer. Clin Cancer Res. 2010;16:5900–5907.
  • Owonikoko TK, Dahlberg SE, Khan SA, et al. A phase 1 safety study of veliparib combined with cisplatin and etoposide in extensive stage small cell lung cancer: A trial of the ECOG-ACRIN cancer research group (E2511). Lung Cancer. 2015;89:66–70.
  • Lallo A, Frese KK, Morrow C, et al. The combination of the PARP inhibitor olaparib and the Wee1 inhibitor AZD1775 as a new therapeutic option for small cell lung cancer. Clin Cancer Res. 2018;24(20):5153–5164.
  • Sen T, Tong P, Stewart CA, et al. CHK1 inhibition in small-cell lung cancer produces single-agent activity in biomarker-defined disease subsets and combination activity with cisplatin or olaparib. Cancer Res. 2017;77:3870–3884.
  • Rudin CM, Pietanza MC, Bauer TM, 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;18:42–51.
  • Carbone DP, Morgenstern D, Le Moulec S, 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:abstr 8507.
  • Gray JE, Heist RS, Starodub AN, et al. Therapy of small cell lung cancer (SCLC) with a topoisomerase-I-inhibiting Antibody-Drug Conjugate (ADC) Targeting Trop-2, Sacituzumab Govitecan. Clin Cancer Res. 2017;23:5711–5719.
  • Edelman MJ, Clamon G, Kahn D, et al. Targeted radiopharmaceutical therapy for advanced lung cancer: phase I trial of rhenium Re188 P2045, a somatostatin analog. J Thorac Oncol. 2009;4:1550–1554.
  • Cheng Y, Wang Q, Li K, et al. Anlotinib as third-line or further-line treatment in relapsed SCLC: a multicentre, randomized, double-blind phase 2 trial. WCLC. 2018;Toronto:abstr OA13.03.
  • Hwang DH, Sun H, Rodig SJ, et al. Myc protein expression correlates with MYC amplification in small-cell lung carcinoma. Histopathology. 2015;67:81–89.
  • Alves Rde C, Meurer RT, Roehe AV. MYC amplification is associated with poor survival in small cell lung cancer: a chromogenic in situ hybridization study. J Cancer Res Clin Oncol. 2014;140:2021–2025.
  • Vader G, Lens SM. The Aurora kinase family in cell division and cancer. Biochim Biophys Acta. 2008;1786:60–72.
  • Melichar B, Adenis A, Lockhart AC, et al. Safety and activity of alisertib, an investigational aurora kinase A inhibitor, in patients with breast cancer, small-cell lung cancer, non-small-cell lung cancer, head and neck squamous-cell carcinoma, and gastro-oesophageal adenocarcinoma: a five-arm phase 2 study. Lancet Oncol. 2015;16:395–405.
  • Niu H, Shin H, Gao F, et al. Aurora a functional single nucleotide polymorphism (SNP) correlates with clinical outcome in patients with advanced solid tumors treated with alisertib, an investigational aurora a kinase inhibitor. EBioMedicine. 2017;25:50–57.
  • Owonikoko TK, Nackaerts K, Csoszi T, et al. OA05.05 randomized phase 2 study: alisertib (MLN8237) or Placebo + Paclitaxel as Second-Line Therapy for Small-Cell Lung Cancer (SCLC). J Thorac Oncol. 2017;12:S261–S2.
  • Helfrich BA, Kim J, Gao D, et al. Barasertib (AZD1152), a small molecule Aurora B inhibitor, inhibits the growth of SCLC cell lines in vitro and in vivo. Mol Cancer Ther. 2016;15:2314–2322.
  • Calvo E, Moreno V, Flynn M, et al. Antitumor activity of lurbinectedin (PM01183) and doxorubicin in relapsed small-cell lung cancer: results from a phase I study. Ann oncol. 2017;28:2559–2566.
  • Pietanza MC, Litvak AM, Varghese AM, et al. A phase I trial of the hedgehog inhibitor, sonidegib (LDE225), in combination with etoposide and cisplatin for the initial treatment of extensive stage small cell lung cancer. Lung Cancer. 2016;99:23–30.
  • Belani CP, Dahlberg SE, Rudin CM, et al. Vismodegib or cixutumumab in combination with standard chemotherapy for patients with extensive-stage small cell lung cancer: a trial of the ECOG-ACRIN Cancer Research Group (E1508). Cancer. 2016;122:2371–2378.
  • Pujol JL, Lavole A, Quoix E, et al. Randomized phase II-III study of bevacizumab in combination with chemotherapy in previously untreated extensive small-cell lung cancer: results from the IFCT-0802 trialdagger. Ann oncol. 2015;26:908–914.
  • Spigel DR, Townley PM, Waterhouse DM, et al. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011;29:2215–2222.
  • Tiseo M, Boni L, Ambrosio F, et al. Italian, multicenter, phase iii, randomized study of cisplatin plus etoposide with or without bevacizumab as first-line treatment in extensive-disease small-cell lung cancer: the GOIRC-AIFA FARM6PMFJM trial. J Clin Oncol. 2017;35:1281–1287.
  • Han JY, Kim HY, Lim KY, et al. A phase II study of nintedanib in patients with relapsed small cell lung cancer. Lung Cancer. 2016;96:108–112.
  • Ready NE, Pang HH, Gu L, et al. Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small-cell lung cancer: a randomized, double-blind, placebo-controlled phase II study-CALGB 30504 (alliance). J Clin Oncol. 2015;33:1660–1665.
  • Allen JW, Moon J, Redman M, et al. Southwest oncology group S0802: a randomized, phase II trial of weekly topotecan with and without ziv-aflibercept in patients with platinum-treated small-cell lung cancer. J Clin Oncol. 2014;32:2463–2470.
  • Mountzios G, Emmanouilidis C, Vardakis N, et al. Paclitaxel plus bevacizumab in patients with chemoresistant relapsed small cell lung cancer as salvage treatment: a phase II multicenter study of the hellenic oncology research group. Lung Cancer. 2012;77:146–150.
  • Spigel DR, Waterhouse DM, Lane S, et al. Efficacy and safety of oral topotecan and bevacizumab combination as second-line treatment for relapsed small-cell lung cancer: an open-label multicenter single-arm phase II study. Clin Lung Cancer. 2013;14:356–363.
  • Trafalis DT, Alifieris C, Stathopoulos GP, et al. Phase II study of bevacizumab plus irinotecan on the treatment of relapsed resistant small cell lung cancer. Cancer Chemother Pharmacol. 2016;77:713–722.
  • Shinmura K, Iwaizumi M, Igarashi H, et al. Induction of centrosome amplification and chromosome instability in p53-deficient lung cancer cells exposed to benzo[a]pyrene diol epoxide (B[a]PDE). J Pathol. 2008;216:365–374.
  • Wistuba II, Behrens C, Virmani AK, et al. High resolution chromosome 3p allelotyping of human lung cancer and preneoplastic/preinvasive bronchial epithelium reveals multiple, discontinuous sites of 3p allele loss and three regions of frequent breakpoints. Cancer Res. 2000;60:1949–1960.
  • Wistuba II, Gazdar AF. Lung cancer preneoplasia. Annu Rev Pathol. 2006;1:331–348.
  • Hussain SP, Amstad P, Raja K, et al. Mutability of p53 hotspot codons to benzo(a)pyrene diol epoxide (BPDE) and the frequency of p53 mutations in nontumorous human lung. Cancer Res. 2001;61:6350–6355.
  • Brambilla E, Gazzeri S, Lantuejoul S, et al. p53 mutant immunophenotype and deregulation of p53 transcription pathway (Bcl2, Bax, and Waf1) in precursor bronchial lesions of lung cancer. Clin Cancer Res. 1998;4:1609–1618.
  • Roberts SA, Lawrence MS, Klimczak LJ, et al. An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers. Nat Genet. 2013;45:970–976.
  • Alexandrov LB, Nik-Zainal S, Wedge DC, et al. Signatures of mutational processes in human cancer. Nature. 2013;500:415–421.
  • Yu H, Batenchuk C, Badzio A, et al. PD-L1 expression by two complementary diagnostic assays and mrna in situ hybridization in small cell lung cancer. J Thorac Oncol. 2017;12:110–120.
  • Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373:1627–1639.
  • Gozzard P, Woodhall M, Chapman C, et al. Paraneoplastic neurologic disorders in small cell lung carcinoma: A prospective study. Neurology. 2015;85:235–239.
  • Wang W, Hodkinson P, McLaren F, et al. Histologic assessment of tumor-associated CD45(+) cell numbers is an independent predictor of prognosis in small cell lung cancer. Chest. 2013;143:146–151.
  • Koyama K, Kagamu H, Miura S, et al. Reciprocal CD4+ T-cell balance of effector CD62Llow CD4+ and CD62LhighCD25+ CD4+ regulatory T cells in small cell lung cancer reflects disease stage. Clin Cancer Res. 2008;14:6770–6779.
  • Tani T, Tanaka K, Idezuka J, et al. Regulatory T cells in paraneoplastic neurological syndromes. J Neuroimmunol. 2008;196:166–169.
  • Reck M, Rodriguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375:1823–1833.
  • Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373:123–135.
  • 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;387:1540–1550.
  • Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemoradiotherapy in stage iii non-small-cell lung cancer. N Engl J Med. 2017;377:1919–1929.
  • Giaccone G, Debruyne C, Felip E, 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;23:6854–6864.
  • Krug LM, Ragupathi G, Hood C, et al. Vaccination of patients with small-cell lung cancer with synthetic fucosyl GM-1 conjugated to keyhole limpet hemocyanin. Clin Cancer Res. 2004;10:6094–6100.
  • Krug LM, Ragupathi G, Hood C, 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;61:9–18.
  • Zarogoulidis K, Ziogas E, Boutsikou E, et al. Immunomodifiers in combination with conventional chemotherapy in small cell lung cancer: a phase II, randomized study. Drug Des Devel Ther. 2013;7:611–617.
  • Terazaki Y, Yoshiyama K, Matsueda S, et al. Immunological evaluation of personalized peptide vaccination in refractory small cell lung cancer. Cancer Sci. 2012;103:638–644.
  • Sakamoto S, Yamada T, Terazaki Y, et al. Feasibility study of personalized peptide vaccination for advanced small cell lung cancer. Clin Lung Cancer. 2017;18:e385–e94.
  • Antonia SJ, Mirza N, Fricke I, et al. Combination of p53 cancer vaccine with chemotherapy in patients with extensive stage small cell lung cancer. Clin Cancer Res. 2006;12:878–887.
  • Pillai RN, Aisner J, Dahlberg SE, 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;74:177–183.
  • Reck M, Luft A, Szczesna A, 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;34:3740–3748.
  • 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;35:3823–3829.
  • Gadgeel SM, Pennell NA, Fidler MJ, et al. Phase II study of maintenance pembrolizumab in patients with extensive-stage small cell lung cancer (SCLC). J Thorac Oncol. 2018;13(9):1393–1399.
  • Chung H, Lopez-Martin JA, Kao SC, et al. Phase 2 study of pembrolizumab in advanced small-cell lung cancer (SCLC): KEYNOTE-158. J Clin Oncol. 2018;36:abstr 8506.
  • Goldman JW, Dowlati A, Antonia S, et al. Safety and antitumor activity of durvalumab monotherapy in patients with pretreated extensive disease small-cell lung cancer (ED-SCLC). J Clin Oncol. 2018;36:abstr 8518.
  • Pujol JL, Greillier L, Audigier-Valette C, 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):viii596–viii602.
  • Rivalland G, Walkiewicz M, Wright G, et al. Small cell lung cancer: the immune microenvironment and prognostic impact of checkpoint expression. J Clin Oncol. 2017;35:abstract 8569.
  • Horn L, Mansfield AS, Szczesna A, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. sep 25 2018. epub ahead of print. DOI:10.1056/NEJMoa18090964
  • 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;17:883–895.
  • Hellman M, Ott PA, Zugazagoitia J, 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:abstract 8503.
  • Antonia S, Callahan MK, Awad MM, et al. OA 07.03a - impact of tumor mutation burden on the efficacy of nivolumab or nivolumab + ipilimumab in small cell lung cancer: an exploratory analysis of checkmate 032. J Thorac Oncol. 2017;11:abstrOA 07.3a.
  • Bondarenko I, Juan-Vidal O, Pajkos G, et al. Preliminary efficacy of durvalumab plus tremelimumab in platinum-refractory/resistant ED-SCLC from Arm A of the Phase II BALTIC study. Ann oncol. 2018;29(suppl_8):viii596–viii602.
  • Thomas M, Ponce Aix S, Navarro Mendivil A, et al. 1527O - 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:v539–v42.
  • Pechoux CL, Sun A, Slotman BJ, et al. Prophylactic cranial irradiation for patients with lung cancer. Lancet Oncol. 2016;17:e277–e93.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.