PD-1/PD-L1 blockade in cancer treatment: perspectives and issues

International Journal of Clinical Oncology

Volumn 21, Issue 3, 2016, Pages 462-473

  Hamanishi, Junzo ^a   Mandai, Masaki ^b   Matsumura, Noriomi ^a   Abiko, Kaoru ^a   Baba, Tsukasa ^a   Konishi, Ikuo ^a  

^a KYOTO UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^b KINKI UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

Biomarker; Immunotherapy; Nivolumab; PD 1; PD L1; Value

Indexed keywords

AMP 224; AMP 514; ANTINEOPLASTIC AGENT; ATEZOLIZUMAB; AVELUMAB; BIOLOGICAL MARKER; BMS 936559; CARBOPLATIN; DACARBAZINE; DOCETAXEL; DURVALUMAB; EVEROLIMUS; IPILIMUMAB; NIVOLUMAB; PACLITAXEL; PEMBROLIZUMAB; PIDILIZUMAB; PROGRAMMED DEATH 1 LIGAND 1; PROGRAMMED DEATH 1 RECEPTOR; UNCLASSIFIED DRUG; MONOCLONAL ANTIBODY; TUMOR MARKER;

ADVANCED CANCER; ANTINEOPLASTIC ACTIVITY; BLADDER CANCER; BREAST CANCER; CANCER SURVIVAL; CANCER THERAPY; COLON CANCER; DIARRHEA; DRUG WITHDRAWAL; ESOPHAGUS CANCER; FOLLICULAR LYMPHOMA; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HODGKIN DISEASE; HUMAN; KIDNEY CARCINOMA; LARGE CELL LYMPHOMA; LIVER CELL CARCINOMA; LIVER DYSFUNCTION; LUNG CANCER; MELANOMA; METASTATIC MELANOMA; NON SMALL CELL LUNG CANCER; NONHODGKIN LYMPHOMA; OVARY CANCER; OVERALL SURVIVAL; PNEUMONIA; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PRURITUS; RASH; REVIEW; STOMACH CANCER; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; TRIPLE NEGATIVE BREAST CANCER; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL (TOPIC); IMMUNOLOGY; IMMUNOTHERAPY; NEOPLASMS; TUMOR ESCAPE; TUMOR MICROENVIRONMENT;

ANTIBODIES, MONOCLONAL; ANTIGENS, CD274; BIOMARKERS, TUMOR; CLINICAL TRIALS AS TOPIC; HUMANS; IMMUNOTHERAPY; NEOPLASMS; PROGRAMMED CELL DEATH 1 RECEPTOR; T-LYMPHOCYTES; TUMOR ESCAPE; TUMOR MICROENVIRONMENT;

EID: 84959140755     PISSN: 13419625     EISSN: 14377772     Source Type: Journal    
DOI: 10.1007/s10147-016-0959-z     Document Type: Review

References (94)

1. Dunn GP, Bruce AT, Ikeda H et al (2002) Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 11:991–998
2. Ishida Y, Agata Y, Shibahara K et al (1992) Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J 11:3887–3895
3. Iwai Y, Ishida M, Tanaka Y et al (2002) Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci USA 99:12293–12297
4. Iwai Y, Terawaki S, Honjo T (2005) PD-1 blockade inhibits hematogenous spread of poorly immunogenic tumor cells by enhanced recruitment of effector T cells. Int Immunol 17:133–144
5. Hirano F, Kaneko K, Tamura H et al (2005) Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res 65:1089–1096
6. Freeman GJ, Long AJ, Iwai Y et al (2000) Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192:1027–1034
7. Okazaki T, Honjo T (2007) PD-1 and PD-1 ligands: from discovery to clinical application. Int Immunol 19:813–824
8. Dong H, Strome SE, Salomao DR et al (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 8:793–800
9. Keir ME, Butte MJ, Freeman GJ et al (2008) PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 26:677–704
10. Blank C, Brown I, Peterson AC et al (2004) PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+ T cells. Cancer Res 64:1140–1145
11. Curiel TJ, Wei S, Dong H et al (2003) Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med 9:562–567
12. Thompson RH, Gillett MD, Cheville JC et al (2004) Costimulatory B7-H1 in renal cell carcinoma patients: indicator of tumor aggressiveness and potential therapeutic target. Proc Natl Acad Sci USA 101:17174–17179
13. Ohigashi Y, Sho M, Yamada Y et al (2005) Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer. Clin Cancer Res 11:2947–2953
14. Hamanishi J, Mandai M, Iwasaki M et al (2007) Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc Natl Acad Sci USA 104:3360–3365
15. Nomi T, Sho M, Akahori T et al (2007) Clinical significance and therapeutic potential of the programmed death-1 ligand/programmed death-1 pathway in human pancreatic cancer. Clin Cancer Res 13:2151–2157
16. Konishi J, Yamazaki K, Azuma M et al (2004) B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression. Clin Cancer Res 10:5094–5100
17. Wu C, Zhu Y, Jiang J et al (2006) Immunohistochemical localization of programmed death-1 ligand-1 (PD-L1) in gastric carcinoma and its clinical significance. Acta Histochem 108:19–24
18. Ghebeh H, Mohammed S, Al-Omair A et al (2006) The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: correlation with important high-risk prognostic factors. Neoplasia 8:190–198
19. Brahmer JR, Drake CG, Wollner I et al (2010) Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol 28:3167–3175
20. Topalian SL, Hodi FS, Brahmer JR et al (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366:2443–2454
21. Topalian SL, Sznol M, McDermott DF et al (2014) Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol 32:1020–1030
22. Robert C, Long GV, Brady B et al (2015) Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 372:320–330
23. Weber JS, D’Angelo SP, Minor D et al (2015) Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol 16:375–384
24. Robert C, Schachter J, Long GV et al (2015) Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 372:2521–2532
25. Brahmer JR, Tykodi SS, Chow LQ et al (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366:2455–2465
26. Lutzky J, Antonia SJ, Blake-Haskins A et al. (2014) A phase 1 study of MEDI4736, an anti-PD-L1 antibody, in patients with advanced solid tumors. 2014 ASCO Annual Meeting. J Clin Oncol 32:5s (suppl: abstr 3001)
27. Herbst RS, Soria JC, Kowanetz M et al (2014) Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature (Lond) 515:563–567
28. Rizvi NA, Mazières J, Planchard D et al (2015) Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol 16:257–265
29. Brahmer J, Reckamp KL, Baas P et al (2015) Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 373:123–135
30. Borghaei H, Paz-Ares L, Horn L et al (2015) Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 373:1627–1639
31. Clinical Trials. gov. NCT02041533
32. Brahmer JR, Rizvi NA, Lutzky J et al. (2014) Clinical activity and biomarkers of MEDI4736, an anti-PD-L1 antibody, in patients with NSCLC. 2014 ASCO Annual Meeting. J Clin Oncol 32:5s (suppl: abstr 8021)
33. Gulley JL, Spigel D, Kelly K et al. (2015) Avelumab (MSB0010718C), an anti-PD-L1 antibody, in advanced NSCLC patients: a phase 1b, open-label expansion trial in patients progressing after platinum-based chemotherapy. 2015 ASCO Annual Meeting. J Clin Oncol 33 (suppl: abstr 8034)
34. Motzer RJ, Rini BI, McDermott DF et al (2015) Nivolumab for metastatic renal cell carcinoma: results of a randomized phase II trial. J Clin Oncol 33:1430–1437
35. Motzer RJ, Escudier B, McDermott DF et al (2015) Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 373:1803–1813
36. Hamanishi J, Mandai M, Matsumura N et al (2010) Activated local immunity by CC chemokine ligand 19-transduced embryonic endothelial progenitor cells suppresses metastasis of murine ovarian cancer. Stem Cells 28:164–173
37. Hamanishi J, Mandai M, Abiko K et al (2011) The comprehensive assessment of local immune status of ovarian cancer by the clustering of multiple immune factors. Clin Immunol 141:338–347
38. Hamanishi J, Mandai M, Ikeda T et al. (2014) Efficacy and safety of anti-PD-1 antibody (Nivolumab: BMS-936558, ONO-4538) in patients with platinum-resistant ovarian cancer. 2014 ASCO Annual Meeting, Clinical Science Symposium. J Clin Oncol 32:5s (suppl: abstr 5511)
39. Hamanishi J, Mandai M, Ikeda T et al (2015) Efficacy and safety of anti-PD-1 antibody (Nivolumab: BMS-936558, ONO-4538) in patients with platinum-resistant ovarian cancer. J Clin Oncol 33:4015–4022
40. Hamanishi J, Mandai M, Ikeda T, et al. (2015) Durable tumor remission in patients with platinum-resistant ovarian cancer receiving nivolumab. 2015 ASCO Annual Meeting. J Clin Oncol 33 (suppl: abstr 5570)
41. Hamanishi J (2015) Immunotherapy for gynaecological cancers: Challenges and opportunities. ESMO Asia 2015. Special Symposium. 18 December 2015, Singapore
42. Varga A, Piha-Paul SA, Ott PA et al. (2015) Antitumor activity and safety of pembrolizumab in patients (pts) with PD-L1 positive advanced ovarian cancer: interim results from a phase Ib study. 2015 ASCO Annual Meeting. J Clin Oncol 33 (suppl: abstr 5510)
43. Disis ML, Patel MR, Pant S et al. (2015) Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with previously treated, recurrent or refractory ovarian cancer: a phase Ib, open-label expansion trial. 2015 ASCO Annual Meeting. J Clin Oncol 33 (suppl: abstr 5509)
44. Seiwert TY, Burtness B, Weiss J et al. (2014) A phase Ib study of MK-3475 in patients with human papilloma virus (HPV)-associated and non-HPV-associated head and neck (H/N) cancer. 2014 ASCO Annual Meeting. J Clin Oncol 32:5s (suppl: abstr 6011)
45. Segal NH, Antonia SJ, Brahmer JR, et al. (2014) Preliminary data from a multi-arm expansion study of MEDI4736, an anti-PD-L1 antibody. 2014 ASCO Annual Meeting. J Clin Oncol 32:5s (suppl: abstr 3002)
46. Plimack ER, Gupta S, Bellmunt J et al. (2014) Phase 1B study of pembrolizumab (pembro; MK-3475) in patients (pts) with advanced urothelial tract cancer. Ann Oncol (Meeting Abstracts) 25:LBA23A
47. Powles T, Eder JP, Fine GD et al (2014) MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature (Lond) 515:558–562
48. Bang YJ, Chung HC, Shankaran V, et al. (2015) Relationship between PD-L1 expression and clinical outcomes in patients with advanced gastric cancer treated with the anti-PD-1 monoclonal antibody pembrolizumab (MK-3475) in KEYNOTE-012. 2015 ASCO Annual Meeting. J Clin Oncol 33 (suppl: abstr 4001)
49. Le DT, Uram JN, Wang H et al (2015) PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372:2509–2520
50. Doi T, Piha-Paul SA, Jalal SI, et al. (2015) Pembrolizumab (MK-3475) for patients (pts) with advanced esophageal carcinoma. Preliminary results from KEYNOTE-028. 2015 ASCO Annual Meeting. J Clin Oncol 33 (suppl: abstr 4010)
51. El-Khoueiry AB, Melero I, Crocenzi TS et al. (2015) Phase I/II safety and antitumor activity of nivolumab in patients with advanced hepatocellular carcinoma (HCC): CA209-040. 2015 ASCO Annual Meeting. J Clin Oncol 33 (suppl: abstr LBA101)
52. Nanda R, Chow L, Dees E, et al. (2014) A phase Ib study of pembrolizumab (MK-3475) in patients with advanced triple-negative breast cancer. San Antonio Breast Cancer Symposium, 2014 December 9–13, San Antonio, TX
53. Emens L, Braiteh F, Cassier P et al. (2014) Inhibition of PD-L1 by MPDL3280A leads to clinical activity in patients with metastatic triple-negative breast cancer. 2014 San Antonio Breast Cancer Symposium, 2014 December 9–13, San Antonio, TX
54. Ansell SM, Lesokhin AM, Borrello I et al (2015) PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med 372:311–319
55. Moskowitz C, Ribrag V, Michot J-M, et al. (2014) PD-1 Blockade with the monoclonal antibody pembrolizumab (MK-3475) in patients with classical Hodgkin lymphoma after brentuximab vedotin failure: preliminary results from a phase 1b study (KEYNOTE-013). 56th Annual Meeting of the American Society of Hematology, December 6–9, 2014 (abstr 290)
56. Lesokhin AM, Ansell SM, Armand P et al. (2014) Preliminary results of a phase I study of nivolumab (BMS-936558) in patients with relapsed or refractory lymphoid malignancies. 56th Annual Meeting of the American Society of Hematology, December 6–9, 2014 (abstr 291)
57. Chinai JM, Janakiram M, Chen F et al (2015) New immunotherapies targeting the PD-1 pathway. Trends Pharmacol Sci 36:587–595
58. Clinical Trials. gov. NCT02484404
59. Clinical Trials. gov. NCT02599779
60. Larkin J, Chiarion-Sileni V, Gonzalez R et al (2015) Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373:23–34
61. Hammers HJ, Plimack ER, Infante JR, et al. (2015) Phase I study of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma (mRCC). 2015 ASCO Annual Meeting. J Clin Oncol 32 (suppl: abstr 4504)
62. Patnaik A, Socinski MA, Gubens MA et al.(2015) Phase 1 study of pembrolizumab (pembro; MK-3475) plus ipilimumab (IPI) as second-line therapy for advanced non-small cell lung cancer (NSCLC): KEYNOTE-021 cohort D. 2015 ASCO Annual Meeting. J Clin Oncol 33 (suppl: abstr 8011)
63. Clinical Trials. gov. NCT02498600
64. Clinical Trials. gov. NCT01968109
65. Clinical Trials. gov. NCT01714739
66. Clinical Trials. gov. NCT02221960
67. Clinical Trials. gov. NCT02253992
68. Clinical Trials. gNCT02466568
69. Callahan M. (2015) Understanding the biology behind responses to immunotherapy. 2014 ASCO Annual Meeting. Developmental therapeutics—immunotherapy (Oral Abstract Session as discussant)
70. Lipson EJ, Forde PM, Hammers HJ et al (2015) Antagonists of PD-1 and PD-L1 in cancer treatment. Antagonists of PD-1 and PD-L1 in cancer treatment. Semin Oncol 42:587–600
71. Taube JM, Anders RA, Young GD et al (2012) Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med 4:127–137
72. Garber K (2015) Predictive biomarkers for checkpoints, first tests approved. Nat Biotechnol 33:1217–1218
73. Peng J, Hamanishi J, Matsumura N et al (2015) Chemotherapy induces programmed cell death-ligand 1 overexpression via the nuclear factor-κB to foster an immunosuppressive tumor microenvironment in ovarian cancer. Cancer Res 75:5034–5045
74. Abiko K, Mandai M, Hamanishi J et al (2013) PD-L1 on tumor cells is induced in ascites and promotes peritoneal dissemination of ovarian cancer through CTL dysfunction. Clin Cancer Res 16:1363–1374
75. Chen L, Han X (2015) Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future. J Clin Invest 125:3384–3391
76. Antonia SJ, Bendell JC, Taylor MH, et al. (2015) Phase I/II study of nivolumab with or without ipilimumab for treatment of recurrent small cell lung cancer (SCLC): CA209-032. 2015 ASCO Annual Meeting. J Clin Oncol 33 (suppl: abstr 7503)
77. Alexandrov LB, Nik-Zainal S, Wedge DC et al (2013) Signatures of mutational processes in human cancer. Nature (Lond) 500:415–421
78. Pardoll M (2015) The ABCs of cancer immunotherapy. 2015 ASCO Annual Meeting, Education Session
79. Postow MA, Callahan MK, Wolchok JD (2015) Immune checkpoint blockade in cancer therapy. J Clin Oncol 33:1974–1982
80. Gubin MM, Zhang X, Schuster H et al (2014) Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature (Lond) 515:577–581
81. Snyder A, Makarov V, Merghoub T et al (2014) Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med 371:2189–2199
82. Rizvi NA, Hellmann MD, Snyder KA et al (2015) Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 348:124–128
83. Naidoo J, Page DB, Li BT et al (2015) Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol 26:2375–2391
84. Champiat S, Lambotte O, Barreau E, et al. (2015) Management of Immune Checkpoint Blockade Dysimmune Toxicities: a collaborative position paper. Ann Oncol. pii: mdv623 [Epub ahead of print]
85. Weber JS, Antonia SJ, Topalian SL, et al. (2015) Safety profile of nivolumab (NIVO) in patients (pts) with advanced melanoma (MEL): a pooled analysis. 2015 ASCO Annual Meeting. J Clin Oncol 33 (suppl: abstr 9018)
86. Highlights of prescribing information of nivolumab http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125554lbl.pdf
87. Highlights of prescribing information of pembrolizumab. http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125514s004s006lbl.pdf
88. Postow MA (2015) Managing immunotherapy-related side effects. 2015 ASCO Annual Meeting. The ABCs of Cancer Immunotherapy
89. Sanlorenzo M, Vujic I, Daud A et al (2015) Pembrolizumab cutaneous adverse events and their association with disease progression. JAMA Dermatol 151:1206–1212
90. Saltz L (2015) Perspectives on Value. 2015 ASCO Annual Meeting, Plenary Session Including the Science of Oncology Award and Lecture
91. Schnipper LE, Davidson NE, Wollins DS et al (2015) American Society of Clinical Oncology Statement: a conceptual framework to assess the value of cancer treatment options. J Clin Oncol 33:2563–2577
92. Burnet FM (1967) Immunological aspects of malignant disease. Lancet 1:1171–1174
93. Dunn GP, Bruce AT, Ikeda H et al (2002) Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 3:991–998
94. Schreiber RD, Old LJ, Smyth MJ (2011) Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science 331:1565–1570