Tuberc Respir Dis.  2014 Sep;77(3):111-115. 10.4046/trd.2014.77.3.111.

Immunotherapy for Non-Small Cell Lung Cancer

• Yoon SH

• KMID: 2320556
• DOI: http://doi.org/10.4046/trd.2014.77.3.111

Abstract

Lung cancer is the leading cause of cancer-related mortality worldwide, and more than 80% of cases are of non-small cell lung cancer. Although chemotherapy and molecularly targeted therapy may provide some benefit, there is a need for newer therapies for the treatment of patients with advanced NSCLC. Immunotherapy aims to augment the recognition of cancer as foreign, to stimulate immune responsiveness, and to relieve the inhibition of the immune response that allows tolerance to tumor survival and growth. Two immunotherapeutic approaches showing promise in NSCLC are immune checkpoint inhibition and cancer vaccination. Although currently immunotherapy does not have an established role in the treatment of NSCLC, these patients should be enrolled in formal clinical trials.

Keyword

Carcinoma, Non-Small-Cell Lung; Immunotherapy; Cancer Vaccines

MeSH Terms

Cancer Vaccines
Carcinoma, Non-Small-Cell Lung*
Drug Therapy
Humans
Immunotherapy*
Lung Neoplasms
Mortality
Vaccination
Cancer Vaccines

Reference

1. Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, et al. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2012; 30:2046–2054.

2. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012; 366:2443–2454.

3. Brahmer JR, Horn L, Antonia SJ, Spigel D, Ghandi L, Sequist LV, et al. Nivolumab (anti-PD-1; BMS-936558; ONO-4538) in patients with non-small cell lung cancer (NSCLC): overall survival and long-term safety in a phase 1 trial. In : IASLC 15th World Conference on Lung Cancer; 2013 Oct 27-30; Sydney, Australia. MO18.03.

4. Antonia SJ, Grosso JF, Horak CE, Harbison CT, Kurland JF, Inzunza HD, et al. Association of tumor PD-L1 expression and immune biomarkers with clinical activity in patients with non-small cell lung cancer (NSCLC) treated with nivolumab (ANTI-PD-1; BMS-936558; ONO-4538). In : IASLC 15th World Conference on Lung Cancer; 2013 Oct 27-30; Sydney, Australia. P2.11-035.

5. Garon EB, Balmanoukian A, Hamid O, Hui R, Gandhi L, Leighl N. Preliminary clinical safety and activity of MK-3475 monotherapy for the treatment of previously treated patients with non-small cell lung cancer (NSCLC). In : IASLC 15th World Conference on Lung Cancer; 2013 Oct 27-30; Sydney, Australia. MO18.02.

6. Spigel DR, Gettinger SN, Horn L, Herbst RS, Gandhi L, Gordon MS, et al. Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). J Clin Oncol. 2013; 31:Suppl. Abstr 8008.

7. Horn L, Herbst RS, Spiegel D, Gettinger SN, Gordon MS, Hollebecque A, et al. An analysis of the relationship of clinical activity to baseline EGFR status, PD-L1 expression and prior treatment history in patients with non-small cell lung cancer (NSCLC) following PD-L1 blockade with MPDL3280A (anti-PDL1). In : IASLC 14th World Conference on Lung Cancer; 2011 Jul 2-5; Amsterdam, the Netherlands. MO18.01.

8. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012; 366:2455–2465.

9. Khleif SN, Lutzky J, Segal NH, Antonia S, Blake-Haskins A, Stewart R, et al. MEDI4736, an anti-PD-L1 antibody with modified Fc domain: preclinical evaluation and early clinical results from a phase I study in patients with advanced solid tumors. In : Proceedings from the European Cancer Congress 2013; 2013 Sep 27-Oct 1; Amsterdam, The Netherlands. Abstract No. 802.

10. Vansteenkiste J, Zielinski M, Linder A, Dahabreh J, Gonzalez EE, Malinowski W, et al. Adjuvant MAGE-A3 immunotherapy in resected non-small-cell lung cancer: phase II randomized study results. J Clin Oncol. 2013; 31:2396–2403.

11. Ulloa-Montoya F, Louahed J, Dizier B, Gruselle O, Spiessens B, Lehmann FF, et al. Predictive gene signature in MAGE-A3 antigen-specific cancer immunotherapy. J Clin Oncol. 2013; 31:2388–2395.

12. Butts C, Maksymiuk A, Goss G, Soulieres D, Marshall E, Cormier Y, 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; 137:1337–1342.

13. Butts C, Socinski MA, Mitchell PL, Thatcher N, Havel L, Krzakowski M, 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.

14. Nemunaitis J, Dillman RO, Schwarzenberger PO, Senzer N, Cunningham C, Cutler J, et al. Phase II study of belagenpuma-tucel-L, a transforming growth factor beta-2 antisense gene-modified allogeneic tumor cell vaccine in non-small-cell lung cancer. J Clin Oncol. 2006; 24:4721–4730.

15. Nemunaitis J, Nemunaitis M, Senzer N, Snitz P, Bedell C, Kumar P, et al. Phase II trial of Belagenpumatucel-L, a TGF-beta2 antisense gene modified allogeneic tumor vaccine in advanced non small cell lung cancer (NSCLC) patients. Cancer Gene Ther. 2009; 16:620–624.