Generic placeholder image

Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Systematic Review Article

Efficacy and Safety of Antigen-specific Immunotherapy in the Treatment of Patients with Non-small-cell Lung Cancer: A Systematic Review and Meta-analysis

Author(s): Bing-Di Yan, Xiao-Feng Cong, Sha-Sha Zhao, Meng Ren, Zi-Ling Liu, Zhi Li, Chen Chen and Lei Yang*

Volume 19, Issue 3, 2019

Page: [199 - 209] Pages: 11

DOI: 10.2174/1568009618666180430124738

Price: $65

Abstract

Background and Objective: We performed this systematic review and meta-analysis to assess the efficacy and safety of antigen-specific immunotherapy (Belagenpumatucel-L, MAGE-A3, L-BLP25, and TG4010) in the treatment of patients with non-small-cell lung cancer (NSCLC).

Methods: A comprehensive literature search on PubMed, Embase, and Web of Science was conducted. Eligible studies were clinical trials of patients with NSCLC who received the antigenspecific immunotherapy. Pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated for overall survival (OS), progression-free survival (PFS). Pooled risk ratios (RRs) were calculated for overall response rate (ORR) and the incidence of adverse events.

Results: In total, six randomized controlled trials (RCTs) with 4,806 patients were included. Pooled results showed that, antigen-specific immunotherapy did not significantly prolong OS (HR=0.92, 95%CI: 0.83, 1.01; P=0.087) and PFS (HR=0.93, 95%CI: 0.85, 1.01; P=0.088), but improved ORR (RR=1.72, 95%CI: 1.11, 2.68; P=0.016). Subgroup analysis based on treatment agents showed that, tecemotide was associated with a significant improvement in OS (HR=0.85, 95%CI: 0.74, 0.99; P=0.03) and PFS (HR=0.70, 95%CI: 0.49, 0.99, P=0.044); TG4010 was associated with an improvement in PFS (HR=0.87, 95%CI: 0.75, 1.00, P=0.058). In addition, NSCLC patients who were treated with antigen-specific immunotherapy exhibited a significantly higher incidence of adverse events than those treated with other treatments (RR=1.11, 95%CI: 1.00, 1.24; P=0.046).

Conclusion: Our study demonstrated the clinical survival benefits of tecemotide and TG4010 in the treatment of NSCLC. However, these evidence might be limited by potential biases. Therefore, further well-conducted, large-scale RCTs are needed to verify our findings.

Keywords: Non-small-cell lung cancer, antigen-specific immunotherapy, meta-analysis, pooled hazard ratios, TG4010, T-cell activity.

Graphical Abstract
[1]
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127: 2893-917.
[2]
Sher T, Dy GK, Adjei AA. Small cell lung cancer. Mayo Clin Proc 2008; 83: 355-67.
[3]
Goldstraw P, Crowley J, Chansky K, et al. The IASLC lung cancer staging project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol 2007; 2: 706-14.
[4]
Pignon JP, Tribodet H, Scagliotti GV, et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol 2008; 26: 3552-9.
[5]
Jackman DM, Miller VA, Cioffredi LA, et al. Impact of epidermal growth factor receptor and KRAS mutations on clinical outcomes in previously untreated non-small cell lung cancer patients: results of an online tumor registry of clinical trials. Clin Cancer Res 2009; 15: 5267-73.
[6]
Hall RD, Gray JE, Chiappori AA. Beyond the standard of care: a review of novel immunotherapy trials for the treatment of lung cancer. Cancer Contr 2013; 20: 22-31.
[7]
Declerck S, Vansteenkiste J. Immunotherapy for lung cancer: ongoing clinical trials. Future Oncol 2014; 10: 91-105.
[8]
Domingues D, Turner A, Silva MD, et al. Immunotherapy and lung cancer: current developments and novel targeted therapies. Immunotherapy 2014; 6: 1221-35.
[9]
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009; 339: b2535.
[10]
Higgins JP, Altman DG, Gøtzsche PC, et al. The cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011; 343: d5928.
[11]
Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008; 336: 924-6.
[12]
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557-60.
[13]
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177-88.
[14]
Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959; 22: 719-48.
[15]
Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994; 50: 1088-101.
[16]
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629-34.
[17]
Giaccone G, Bazhenova LA, Nemunaitis J, et al. A phase III study of belagenpumatucel-L, an allogeneic tumour cell vaccine, as maintenance therapy for non-small cell lung cancer. Eur J Cancer 2015; 51: 2321-9.
[18]
Vansteenkiste JF, Cho BC, Vanakesa T, et al. Efficacy of the MAGE-A3 cancer immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-positive non-small-cell lung cancer (MAGRIT): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2016; 17: 822-35.
[19]
Vansteenkiste J, Zielinski M, Linder A, et al. Adjuvant MAGE-A3 immunotherapy in resected non-small-cell lung cancer: phase II randomized study results. J Clin Oncol 2013; 31: 2396-403.
[20]
Butts C, Socinski MA, Mitchell PL, et al. Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-cell lung cancer (START): a randomised, double-blind, phase 3 trial. Lancet Oncol 2014; 15: 59-68.
[21]
Butts C, Maksymiuk A, Goss G, et al. Updated survival analysis in patients with stage IIIB or IV non-small-cell lung cancer receiving BLP25 liposome vaccine (L-BLP25): phase IIB randomized, multicenter, open-label trial. J Cancer Res Clin Oncol 2011; 137: 1337-42.
[22]
Quoix E, Ramlau R, Westeel V, et al. Therapeutic vaccination with TG4010 and first-line chemotherapy in advanced non-small-cell lung cancer: a controlled phase 2B trial. Lancet Oncol 2011; 12: 1125-33.
[23]
Mitchell P, Thatcher N, Socinski MA, et al. Tecemotide in unresectable stage III non-small-cell lung cancer in the phase III START study: updated overall survival and biomarker analyses. Ann Oncol 2015; 26: 1134-42.
[24]
Butts C, Murray N, Maksymiuk A, et al. Randomized phase IIB trial of BLP25 liposome vaccine in stage IIIB and IV non-small-cell lung cancer. J Clin Oncol 2005; 23: 6674-81.
[25]
Wang M, Cao JX, Liu YS, et al. Evaluation of tumour vaccine immunotherapy for the treatment of advanced non-small cell lung cancer: a systematic meta-analysis. BMJ Open 2015; 5: e006321.
[26]
Dammeijer F, Lievense LA, Veerman GD, et al. Efficacy of tumor vaccines and cellular immunotherapies in non-small-cell lung cancer: a systematic review and meta-analysis. J Clin Oncol 2016; 34: 3204-12.
[27]
Ding M, Yang J. Therapeutic vaccination for non-small-cell lung cancer: a meta-analysis. Med Oncol 2014; 31: 928.
[28]
Zhou L, Wang XL, Deng QL, Du YQ, Zhao NQ. The efficacy and safety of immunotherapy in patients with advanced NSCLC: a systematic review and meta-analysis. Sci Rep 2016; 6: 32020.
[29]
Gelbard A, Garnett CT, Abrams SI, et al. Combination chemotherapy and radiation of human squamous cell carcinoma of the head and neck augments CTL-mediated lysis. Clin Cancer Res 2006; 12: 1897-905.
[30]
Obeid M, Panaretakis T, Tesniere A, et al. Leveraging the immune system during chemotherapy: moving calreticulin to the cell surface converts apoptotic death from “silent” to immunogenic. Cancer Res 2007; 67: 7941-4.
[31]
Zitvogel L, Kepp O, Senovilla L, Menger L, Chaput N, Kroemer G. Immunogenic tumor cell death for optimal anticancer therapy: the calreticulin exposure pathway. Clin Cancer Res 2010; 16: 3100-4.
[32]
Formenti SC, Demaria S. Combining radiotherapy and cancer immunotherapy: a paradigm shift. J Natl Cancer Inst 2013; 105: 256-65.
[33]
Formenti SC, Demaria S. Systemic effects of local radiotherapy. Lancet Oncol 2009; 10: 718-26.
[34]
Roses RE, Xu M, Koski GK, Czerniecki BJ. Radiation therapy and Toll-like receptor signaling: implications for the treatment of cancer. Oncogene 2008; 27: 200-7.
[35]
Danna EA, Sinha P, Gilbert M, Clements VK, Pulaski BA, Ostrand-Rosenberg S. Surgical removal of primary tumor reverses tumor-induced immunosuppression despite the presence of metastatic disease. Cancer Res 2004; 64: 2205-11.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy