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PMID: 27483468 Published · epublish English Journal Article Meta-Analysis Review Systematic Review

PD-1 Antibody Monotherapy for Malignant Melanoma: A Systematic Review and Meta-Analysis.

PloS one ·Vol. 11 ·No. 8 ·2016-00-00 ·Pages e0160485

Lin Z, Chen X, Li Z, Luo Y, Fang Z, Xu B, Han M

Abstract

Antibodies targeting programmed death 1 (PD-1) help prevent tumor cells from escaping immune-mediated destruction. We conducted this systematic review and meta-analysis to gain insight into the efficacy of PD-1 antibodies for the treatment of melanoma. Five trials involving 2,828 adult patients were included in this meta-analysis. In patients with previously untreated or refractory melanoma, treatment with PD-1 antibodies significantly improved the six-month progression-free survival (PFS) (HR 0.55, 95% CI 0.50-0.60, P<0.00001) and the overall response rate (OR 3.89, 95% CI 3.12-4.83, P<0.00001). This meta-analysis indicated that anti-PD-1 treatment might provide a significant survival benefit in patients with melanoma. In addition, we found that patients treated with nivolumab reported significantly fewer treatment-related adverse events (OR 0.74, 95% CI 0.57-0.97, P = 0.03) than those treated with other agents, but there was a dose-dependent increase in the frequency of adverse events in patients treated with pembrolizumab.

MeSH Terms
Antibodies, Monoclonal/therapeutic use Antibodies, Monoclonal, Humanized/administration & dosage,adverse effects Antineoplastic Agents/therapeutic use Clinical Trials as Topic Diarrhea/diagnosis,etiology,physiopathology Disease-Free Survival Drug Administration Schedule Exanthema/diagnosis,etiology,physiopathology Fatigue/diagnosis,etiology,physiopathology Gene Expression Humans Melanoma/drug therapy,mortality,pathology Nausea/diagnosis,etiology,physiopathology Nivolumab Programmed Cell Death 1 Receptor/antagonists & inhibitors,genetics,immunology Pruritus/diagnosis,etiology,physiopathology Skin Neoplasms/drug therapy,mortality,pathology
Chemicals
Antibodies, Monoclonal Antibodies, Monoclonal, Humanized Antineoplastic Agents PDCD1 protein, human Programmed Cell Death 1 Receptor Nivolumab pembrolizumab
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Lin Zhijuan
Department of Hematology, the First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
Chen Xing
Department of Nephrology, the First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
Li Zhifeng
Department of Hematology, the First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
Luo Yiming
Department of Hematology, the First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
Fang Zhihong
Department of Hematology, the First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
Xu Bing
Department of Hematology, the First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
Han Mingzhe
Department of Hematology, the First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China. | State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China. | Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, and Department of Stem Cells and Regenerative Medicine, Peking Union Medical College, Tianjin, People's Republic of China.
Supplementary Concepts
Melanoma, Cutaneous Malignant (Disease)
References (36)
36 references, click to expand
  1. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer.
    N Engl J Med. 2015 Oct 22;373(17):1627-39 PMID: 26412456
  2. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death.
    EMBO J. 1992 Nov;11(11):3887-95 PMID: 1396582
  3. Escape of human solid tumors from T-cell recognition: molecular mechanisms and functional significance.
    Adv Immunol. 2000;74:181-273 PMID: 10605607
  4. Safety and Antitumor Activity of Anti-PD-1 Antibody, Nivolumab, in Patients With Platinum-Resistant Ovarian Cancer.
    J Clin Oncol. 2015 Dec 1;33(34):4015-22 PMID: 26351349
  5. Melanogenesis affects overall and disease-free survival in patients with stage III and IV melanoma.
    Hum Pathol. 2013 Oct;44(10):2071-4 PMID: 23791398
  6. Inhibition of melanogenesis as a radiation sensitizer for melanoma therapy.
    Int J Cancer. 2008 Sep 15;123(6):1448-56 PMID: 18567001
  7. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
    N Engl J Med. 2012 Jun 28;366(26):2443-54 PMID: 22658127
  8. PD-L1 expression in cancer patients receiving anti PD-1/PD-L1 antibodies: A systematic review and meta-analysis.
    Crit Rev Oncol Hematol. 2016 Apr;100:88-98 PMID: 26895815
  9. Immune based therapy for melanoma.
    Indian J Med Res. 2016 Feb;143(2):135-44 PMID: 27121512
  10. Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target.
    Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17174-9 PMID: 15569934
  11. Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma.
    J Clin Oncol. 2015 Jun 10;33(17 ):1889-94 PMID: 25667295
  12. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma.
    N Engl J Med. 2015 Jan 22;372(4):311-9 PMID: 25482239
  13. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993.
    J Clin Oncol. 1999 Jul;17(7):2105-16 PMID: 10561265
  14. The Changing Landscape of Smoldering Multiple Myeloma: A European Perspective.
    Oncologist. 2016 Mar;21(3):333-42 PMID: 26921288
  15. The future of systemic therapy of melanoma: combinations, predictive biomarkers.
    Oncology (Williston Park). 2015 Feb;29(2):94, 107 PMID: 25683827
  16. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma.
    N Engl J Med. 2015 Nov 5;373(19):1803-13 PMID: 26406148
  17. Nivolumab in previously untreated melanoma without BRAF mutation.
    N Engl J Med. 2015 Jan 22;372(4):320-30 PMID: 25399552
  18. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor.
    Immunity. 1999 Aug;11(2):141-51 PMID: 10485649
  19. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells.
    J Exp Med. 2009 Dec 21;206(13):3015-29 PMID: 20008522
  20. Pembrolizumab versus Ipilimumab in Advanced Melanoma.
    N Engl J Med. 2015 Jun 25;372(26):2521-32 PMID: 25891173
  21. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation.
    J Exp Med. 2000 Oct 2;192(7):1027-34 PMID: 11015443
  22. PD-1 and its ligands in tolerance and immunity.
    Annu Rev Immunol. 2008;26:677-704 PMID: 18173375
  23. Structure and chromosomal localization of the human PD-1 gene (PDCD1).
    Genomics. 1994 Oct;23(3):704-6 PMID: 7851902
  24. 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. 2015 Apr;16(4):375-84 PMID: 25795410
  25. Cancer statistics, 2015.
    CA Cancer J Clin. 2015 Jan-Feb;65(1):5-29 PMID: 25559415
  26. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial.
    Lancet Oncol. 2015 Aug;16(8):908-18 PMID: 26115796
  27. Programmed death-1/programmed death-L1 signaling pathway and its blockade in hepatitis C virus immunotherapy.
    World J Hepatol. 2015 Oct 18;7(23):2449-58 PMID: 26483866
  28. Inhibitors of melanogenesis increase toxicity of cyclophosphamide and lymphocytes against melanoma cells.
    Int J Cancer. 2009 Mar 15;124(6):1470-7 PMID: 19085934
  29. Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study.
    J Clin Oncol. 2016 Jul 20;34(21):2460-7 PMID: 27138582
  30. Melanin content in melanoma metastases affects the outcome of radiotherapy.
    Oncotarget. 2016 Apr 5;7(14 ):17844-53 PMID: 26910282
  31. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer.
    N Engl J Med. 2015 Jul 9;373(2):123-35 PMID: 26028407
  32. Melanin pigmentation in mammalian skin and its hormonal regulation.
    Physiol Rev. 2004 Oct;84(4):1155-228 PMID: 15383650
  33. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma.
    N Engl J Med. 2015 Jul 2;373(1):23-34 PMID: 26027431
  34. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion.
    Nat Med. 2002 Aug;8(8):793-800 PMID: 12091876
  35. Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN-{gamma} and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway.
    Blood. 2007 Jul 1;110(1):296-304 PMID: 17363736
  36. 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 U S A. 2002 Sep 17;99(19):12293-7 PMID: 12218188
Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0160485
Published
2016-00-00
Epub
2016-00-02
Pages
e0160485
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC4970765
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pone.0160485 PMC Full Text View journal details
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