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Reviews

Emerging drugs targeting PD-1 and PD-L1: reality or hope?

, MD, , MD, , MD, , MD, , MD, , MD, , MD & , MD show all

Bibliography

  • GLOBOCAN 2012: lung cancer, estimated incidence, mortality and prevalence worldwide in 2012. Available from: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx
  • Molina JR, Yang P, Cassivi SD, et al. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc 2008;83:584-94
  • National Comprehensive Cancer Network (NCCN) clinical practice guidelines in oncology (NCCN Guideliness). Nonsmall cell lung cancer. Version 3. 2014. Available from: http://www.nccn.com [Accessed 26 May 2014]
  • Sandler A, Yi J, Dahlberg S, et al. Treatment outcomes by tumor histology in Eastern Cooperative Group Study E4599 of bevacizumab with paclitaxel/carboplatin for advanced non-small cell lung cancer. J Thorac Oncol 2010;5(9):1416-23
  • Fukuoka M, Wu YL, Thongprasert S, et al. Biomarker analyses and final overall survival results from a Phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol 2011;29:2866-74
  • Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 2012;13:239-46
  • Yang JC, Schuler MH, Yamamoto N, et al. LUX-Lung 3: A randomized, open-label, Phase III study of afatinib versus pemetrexed and cisplatin as first-line treatment for patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations. J Clin Oncol 2012;32:abstract #LBA7500
  • Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 2013;368(25):2385-94
  • Pfizer reports positive phase 3 study outcome Of XALKORI® (crizotinib) compared to chemotherapy in previously untreated patients with ALK-positive advanced non-small cell lung cancer (NSCLC). Available from: http://www.pfizer.com/news/press-release/ [Last accessed 26 May 2014]
  • Dasanu CA, Sethi N, Ahmed N. Immune alterations and emerging immunotherapeutic approaches in lung cancer. Expert Opin Biol Ther 2012;12:923-37
  • Marincola FM, Jaffee EM, Hicklin DJ, et al. Escape of human solid tumors from T-cell recognition: molecular mechanisms and functional significance. Adv Immunol 2000;74:181-273
  • Mantovani A, Sica A. Macrophages, innate immunity and cancer: balance, tolerance, and diversity. Curr Opin Immunol 2010;22:231-7
  • Ramnath N, Tan D, Li Q, et al. Is downregulation of MHC class I antigen expression in human non-small cell lung cancer associated with prolonged survival? Cancer Immunol Immunother 2006;55(8):891-9
  • Bremnes RM, Al-Shibli K, Donnem T, et al. The role of tumor-infiltrating immune cells and chronic inflammation at the tumor site on cancer development, progression, and prognosis: emphasis on non-small cell lung cancer. J Thorac Oncol 2011;6:824-33
  • Dieu-Nosjean MC, Antoine M, Danel C, et al. Long-term survival for patients with non-small-cell lung cancer with intratumoral lymphoid structures. J Clin Oncol 2008;26:4410-17
  • Hiraoka K, Miyamoto M, Cho Y, et al. Concurrent infiltration by CD8+ T cells and CD4+ T cells is a favourable prognostic factor in non-small-cell lung carcinoma. Br J Cancer 2006;94:275-80
  • Al-Shibli KI, Donnem T, Al-Saad S, et al. Prognostic effect of epithelial and stromal lymphocyte infiltration in non-small cell lung cancer. Clin Cancer Res 2008;14:5220-7
  • Petersen RP, Campa MJ, Sperlazza J, et al. Tumor infiltrating FOXP3+ regulatory T-cells are associated with recurrence in pathologic stage I NSCLC patients. Cancer 2006;107:2866-72
  • Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012;12:252-64
  • Fife BT, Bluestone JA. Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways. Immunol Rev 2008;224:166-82
  • Mu CY, Huang JA, Chen Y, et al. High expression of PD-L1 in lung cancer may contribute to poor prognosis and tumor cells immune escape through suppressing tumor infiltrating dendritic cells maturation. Med Oncol 2011;28(3):682-8
  • Zhang Y, Wang L, Li Y, et al. Protein expression of programmed death 1 ligand 1 and ligand 2 independently predict poor prognosis in surgically resected lung adenocarcinoma. Onco Targets Ther 2014;7:567-73
  • Wölfle SJ, Strebovsky J, Bartz H, et al. PD-L1 expression on tolerogenic APCs is controlled by STAT-3. Eur J Immunol 2011;41(2):413-24
  • Hirahara K, Ghoreschi K, Yang XP, et al. Interleukin-27 priming of Tcells controls IL-17 production in trans via induction of the ligand PD-L1. Immunity 2012;36(6):1017-30
  • Akbay EA, Koyama S, Carretero J, et al. Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Discov 2013;3:1355-63
  • Lynch TJ, Bondarenko I, Luft A, 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;30:2046-54
  • Wolchok JD, Hoos A, O’Day S, et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res 2009;15:7412-20
  • Bristol-Myers Squibb. Trial in squamous non small cell lung cancer subjects comparing ipilimumab plus paclitaxel and carboplatin versus placebo plus paclitaxel and carboplatin. Available from: http://clinicaltrials.gov/show/NCT01285609 NLM identifier: NCT01285609 [Accessed 10 June 2014]
  • Curran MA, Montalvo W, Yagita H, et al. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci USA 2010;107:4275-80
  • Selby M, Engelhardt J, Lu L-S, et al. Antitumor activity of concurrent blockade of immune checkpoint molecules CTLA-4 and PD-1 in preclinical models. J Clin Oncol 2013;31(Suppl):abstract 3061
  • Brahmer JR, 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. Abstr. MO18.03 Available from: https://www.webges.com/cview/library/wclc/home
  • Study of Nivolumab (BMS-936558) in combination with gemcitabine/cisplatin, pemetrexed/cisplatin, carboplatin/paclitaxel, bevacizumab maintenance, erlotinib, ipilimumab or as monotherapy in subjects with stage IIIB/IV non-small cell lung cancer (NSCLC) (CheckMate 012) - NCT01454102. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • Brahmer JR, Horn L, Gandhi L, et al. Nivolumab (anti-PD-1, BMS-936558, ONO-4538) in patients (pts) with advanced non-small-cell lung cancer (NSCLC): Survival and clinical activity by subgroup analysis. J Clin Oncol 2014;32(5 Suppl):abstract 8112
  • Antonia SJ, Brahmer JR, Gettinger SN, et al. Nivolumab (anti-PD-1; BMS-936558, ONO-4538) in combination with platinum-based doublet chemotherapy (PT-DC) in advanced non-small cell lung cancer (NSCLC). J Clin Oncol 2014;32(5 Suppl):abstract 8113
  • Antonia SJ, Gettinger SN, Chow LQM, et al. Nivolumab (anti-PD-1; BMS-936558, ONO-4538) and ipilimumab in first-line NSCLC: interim phase I results. J Clin Oncol 2014;32(5 Suppl):abstract 8023
  • Rizvi NA, Chow LQM, Borghaei H, et al. Safety and response with nivolumab (anti-PD-1; BMS-936558, ONO-4538) plus erlotinib in patients (pts) with epidermal growth factor receptor mutant (EGFR MT) advanced NSCLC. J Clin Oncol 2014;32(5 Suppl):abstract 8022
  • Gettinger SN, Shepherd FA, Antonia SJ, et al. First-line nivolumab (anti-PD-1; BMS-936558, ONO-4538) monotherapy in advanced NSCLC: Safety, efficacy, and correlation of outcomes with PD-L1 status. J Clin Oncol 2014;32(5 Suppl):abstract 8024
  • Study of BMS-936558 (Nivolumab) compared to docetaxel in previously treated advanced or metastatic squamous cell non-small cell lung cancer (NSCLC) (CheckMate 017) - NCT01642004. Available from: http:/https://clinicaltrials.gov/ Last accessed 12 June 2014]
  • Study of BMS-936558 (Nivolumab) compared to docetaxel in previously treated metastatic non-squamous NSCLC (CheckMate 057) - NCT01673867. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • An open-label, randomized, phase 3 trial of nivolumab versus investigator’s choice chemotherapy as first-line therapy for stage IV or recurrent PD-L1+ non-small cell lung cancer (CheckMate 026) - NCT02041533. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • A Safety Trial of Nivolumab (BMS-936558) in subjects with advanced or metastatic non-small cell lung cancer who have progressed during or after receiving at least one prior systemic regimen (CheckMate 153) - NCT02066636. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • Study of pembrolizumab (MK-3475) in participants with progressive locally advanced or metastatic carcinoma, melanoma, or non-small cell lung carcinoma (P07990/MK-3475-001/KEYNOTE-001) - NCT01295827. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • Garon EB, Leighl NB, Rizvi NA, et al. Safety and clinical activity of MK-3475 in previously treated patients (pts) with non-small cell lung cancer (NSCLC). J Clin Oncol 2014;32(5 Suppl):abstract 8020
  • Gandhi L, Balmanoukian A, Hui R, et al. MK-3475 (anti-PD-1 monoclonal antibody) for non-small cell lung cancer (NSCLC): antitumor activity and association with tumor PD-L1 expression [abstract CT105]. Presented at AACR Annual Meeting, San Diego, 2014
  • Rizvi NA, Garon EB, Patnaik A, et al. Safety and clinical activity of MK-3475 as initial therapy in patients with advanced non-small cell lung cancer (NSCLC). J Clin Oncol 2014;32(5 Suppl):abstract 8007
  • Study of two doses of MK-3475 (Pembrolizumab) versus docetaxel in previously-treated participants with non-small cell lung cancer (MK-3475-010/KEYNOTE-010) - NCT01905657. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012;366:2455-65
  • A Phase 1 study of MPDL3280A (an Engineered Anti-PDL1 Antibody) in patients with locally advanced or metastatic solid tumors - NCT01375842. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • Horn L, Herbst RS, Spigel DR, 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). Abstract MO18.01 Available from: https://www.webges.com/cview/library/wclc/home [Accessed 2 December 2013]
  • A Phase 2 Study of MPDL3280A (an Engineered Anti-PDL1 Antibody) in patients with PD-L1 positive locally advanced or metastatic non-small cell lung cancer - "FIR" - NCT01846416. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • A randomized phase 2 study of MPDL3280A (an Engineered Anti-PDL1 Antibody) compared with docetaxel in patients with locally advanced or metastatic non-small cell lung cancer who have failed platinum therapy - "POPLAR" - NCT01903993. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • A Phase 2 study of MPDL3280A (an Engineered Anti-PDL1 Antibody) in patients with pd-l1 positive locally advanced or metastatic non-small cell lung cancer - "BIRCH" - NCT02031458. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • A randomized phase 3 study of MPDL3280A (an Engineered Anti-PDL1 Antibody) compared to docetaxel in patients with locally advanced or metastatic non-small cell lung cancer who have failed platinum therapy - "OAK" - NCT02008227. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • A Phase 1 study to evaluate MEDI4736 - NCT01693562. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • Brahmer JR, Rizvi NA, Lutzky J, et al. Clinical activity and biomarkers of MEDI4736, an anti-PD-L1 antibody, in patients with NSCLC. J Clin Oncol 2014;32(5 Suppl):abstract 8021
  • A Phase 1b Study of MEDI4736 in combination with tremelimumab in subjects with advanced non-small cell lung cancer (D4190C00006) - NCT02000947. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • Pinder MC, Rizvi NA, Goldberg SB, et al. A phase 1b open-label study to evaluate the safety and tolerability of MEDI4736, an anti–PD-L1 antibody, in combination with tremelimumab in subjects with advanced non–small cell lung cancer. J Clin Oncol 2014;32(Suppl):abstract e19137
  • Safety study of IL-21/Anti-PD-1 combination in the treatment of solid tumors - NCT01629758. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • A Phase I study of an Anti-KIR antibody in combination with an anti-PD1 antibody in patients with advanced solid tumors - NCT01714739. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • Brahmer JL. PD-1/PD.L1 blockade for the treatment of NSCLC. Presentation MO9.2; IASCL WCLC 2013. Available from: https://www.webges.com/cview/library/wclc/home [Accessed 2 December 2013]
  • Villaruz LC, Kalyan A, Zarour H, et al. Immunotherapy in lung cancer. Transl Lung Cancer Res 2014;3(1):2-14
  • Phase II Anti-PD1 epigenetic priming study in NSCLC. (NA_00084192) - NCT01928576. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • Study of Nivolumab (BMS-936558) in subjects with advanced or metastatic squamous cell non-small cell lung cancer who have received at least two prior systemic regimens (CheckMate 063) - NCT01721759. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • Study of pembrolizumab (MK-3475) monotherapy in participants with advanced solid tumors and pembrolizumab combination therapy in participants with advanced non-small cell lung cancer (MK-3475-011/KEYNOTE-011) - NCT01840579. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • Study of pembrolizumab (MK-3475) in participants with advanced non-small cell lung cancer (MK-3475-025/KEYNOTE-025) - NCT02007070. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • A study of pembrolizumab (MK-3475) in combination with chemotherapy or immunotherapy in participants with lung cancer (MK-3475-021/KEYNOTE-021) - NCT02039674. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • MK-3475 in melanoma and NSCLC patients with brain metastases - NCT02085070. Available from: http://clinicaltrials.gov/show/NCT02085070
  • Study of pembrolizumab (MK-3475) compared to platinum-based chemotherapies in participants with metastatic non-small cell lung cancer (MK-3475-024/KEYNOTE-024) - NCT02142738. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • Study to assess the safety, tolerability, and pharmacokinetics of amp-224 in patients with advanced cancer - NCT01352884. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • A Phase 1 study to evaluate AMP-514. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • A Phase 1b Study of MPDL3280A (an Engineered Anti-PDL1 Antibody) in combination with tarceva in patients with non-small cell lung cancer - NCT02013219. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • A Phase 1b Study of MPDL3280A (an Engineered Anti-PDL1 Antibody) in combination with cobimetinib in patients with locally advanced or metastatic solid tumors - NCT01988896. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • MEDI4736 (Anti PD-L1) combined with gefitinib in subjects with non-small cell lung cancer (NSCLC) - NCT02088112. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • A global study to assess the effects of MEDI4736 in patients with locally advanced or metastatic non small cell lung cancer (ATLANTIC) - NCT02087423. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • Immune-modulated study of selected small molecules (Gefitinib, AZD9291, or Selumetinib + Docetaxel) or a 1st immune-mediated therapy (IMT; Tremelimumab) With a sequential switch to a 2nd IMT (MEDI4736) in patients with locally advanced or metastatic non-small-cell lung cancer - NCT02179671. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • Lung-MAP: S1400 biomarker-targeted second-line therapy in treating patients with recurrent stage IIIB-IV non-small cell lung cancer - NCT02154490. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • A global study to assess the effects of MEDI4736 following concurrent chemoradiation in patients with stage iii unresectable non-small cell lung cancer (PACIFIC) - NCT02125461. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • MSB0010718C in solid tumors - NCT01772004. Available from: http:/https://clinicaltrials.gov/ [Last accessed 3 July 2014]
  • Heery CR, O’Sullivan Coyne GH, Madan RA, et al. Phase I open-label, multiple ascending dose trial of MSB0010718C, an anti-PD-L1 monoclonal antibody, in advanced solid malignancies. J Clin Oncol 2014;32(5 Suppl):abstract 3064

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