Development of immunotherapy in bladder cancer: present and future on targeting PD(L)1 and CTLA-4 pathways View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-06-01

AUTHORS

Mathieu Rouanne, Mathieu Roumiguié, Nadine Houédé, Alexandra Masson-Lecomte, Pierre Colin, Géraldine Pignot, Stéphane Larré, Evanguelos Xylinas, Morgan Rouprêt, Yann Neuzillet

ABSTRACT

PurposeOver the past 3 decades, no major treatment breakthrough has been reported for advanced bladder cancer. Recent Food and Drug Administration (FDA) approval of five immune checkpoint inhibitors in the management of advanced bladder cancer represent new therapeutic opportunities. This review examines the available data of the clinical trials leading to the approval of ICIs in the management of metastatic bladder cancer and the ongoing trials in advanced and localized settings.MethodsA literature search was performed on PubMed and ClinicalTrials.gov combining the MeSH terms: ‘urothelial carcinoma’ OR ‘bladder cancer’, and ‘immunotherapy’ OR ‘CTLA-4’ OR ‘PD-1’ OR ‘PD-L1’ OR ‘atezolizumab’ OR ‘nivolumab’ OR ‘ipilimumab’ OR ‘pembrolizumab’ OR ‘avelumab’ OR ‘durvalumab’ OR ‘tremelimumab’. Prospectives studies evaluating anti-PD(L)1 and anti-CTLA-4 monoclonal antibodies were included.ResultsEvidence-data related to early phase and phase III trials evaluating the 5 ICIs in the advanced urothelial carcinoma are detailed in this review. Anti-tumour activity of the 5 ICIs supporting the FDA approval in the second-line setting are reported. The activity of PD(L)1 inhibitors in the first-line setting in cisplatin-ineligible patients are also presented. Ongoing trials in earlier disease-states including non-muscle-invasive and muscle-invasive bladder cancer are discussed.ConclusionsBlocking the PD-1 negative immune receptor or its ligand, PD-L1, results in unprecedented rates of anti-tumour activity in patients with metastatic urothelial cancer. However, a large majority of patients do not respond to anti-PD(L)1 drugs monotherapy. Investigations exploring the potential value of predictive biomarkers, optimal combination and sequences are ongoing to improve such treatment strategies. More... »

PAGES

1727-1740

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00345-018-2332-5

DOI

http://dx.doi.org/10.1007/s00345-018-2332-5

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1104333388

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29855698


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26 schema:description PurposeOver the past 3 decades, no major treatment breakthrough has been reported for advanced bladder cancer. Recent Food and Drug Administration (FDA) approval of five immune checkpoint inhibitors in the management of advanced bladder cancer represent new therapeutic opportunities. This review examines the available data of the clinical trials leading to the approval of ICIs in the management of metastatic bladder cancer and the ongoing trials in advanced and localized settings.MethodsA literature search was performed on PubMed and ClinicalTrials.gov combining the MeSH terms: ‘urothelial carcinoma’ OR ‘bladder cancer’, and ‘immunotherapy’ OR ‘CTLA-4’ OR ‘PD-1’ OR ‘PD-L1’ OR ‘atezolizumab’ OR ‘nivolumab’ OR ‘ipilimumab’ OR ‘pembrolizumab’ OR ‘avelumab’ OR ‘durvalumab’ OR ‘tremelimumab’. Prospectives studies evaluating anti-PD(L)1 and anti-CTLA-4 monoclonal antibodies were included.ResultsEvidence-data related to early phase and phase III trials evaluating the 5 ICIs in the advanced urothelial carcinoma are detailed in this review. Anti-tumour activity of the 5 ICIs supporting the FDA approval in the second-line setting are reported. The activity of PD(L)1 inhibitors in the first-line setting in cisplatin-ineligible patients are also presented. Ongoing trials in earlier disease-states including non-muscle-invasive and muscle-invasive bladder cancer are discussed.ConclusionsBlocking the PD-1 negative immune receptor or its ligand, PD-L1, results in unprecedented rates of anti-tumour activity in patients with metastatic urothelial cancer. However, a large majority of patients do not respond to anti-PD(L)1 drugs monotherapy. Investigations exploring the potential value of predictive biomarkers, optimal combination and sequences are ongoing to improve such treatment strategies.
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33 schema:keywords Administration approval
34 CTLA-4 pathway
35 Drug Administration approval
36 FDA approval
37 ICI
38 MeSH terms
39 MethodsA literature search
40 PD-1
41 PD-1 negative immune receptor
42 PD-L1
43 Prospectives studies
44 PubMed
45 PurposeOver
46 ResultsEvidence-data
47 activity
48 advanced bladder cancer
49 advanced urothelial carcinoma
50 anti-CTLA-4 monoclonal antibody
51 anti-tumor activity
52 antibodies
53 approval
54 approval of ICIs
55 available data
56 biomarkers
57 bladder cancer
58 breakthrough
59 cancer
60 carcinoma
61 checkpoint inhibitors
62 cisplatin-ineligible patients
63 clinical trials
64 combination
65 data
66 decades
67 development
68 development of immunotherapy
69 drug monotherapy
70 early phase
71 first-line setting
72 food
73 future
74 immune checkpoint inhibitors
75 immune receptors
76 immunotherapy
77 inhibitors
78 investigation
79 large majority
80 ligands
81 literature search
82 major treatment breakthrough
83 majority
84 management
85 metastatic bladder cancer
86 metastatic urothelial cancer
87 monoclonal antibodies
88 monotherapy
89 muscle-invasive bladder cancer
90 negative immune receptor
91 new therapeutic opportunities
92 ongoing trials
93 opportunities
94 optimal combination
95 pathway
96 patients
97 phase
98 potential value
99 predictive biomarkers
100 rate
101 recent Food
102 receptors
103 review
104 search
105 second-line setting
106 sequence
107 setting
108 strategies
109 study
110 such treatment strategies
111 terms
112 therapeutic opportunities
113 treatment breakthroughs
114 treatment strategies
115 tremelimumab
116 trials
117 unprecedented rate
118 urothelial cancer
119 urothelial carcinoma
120 values
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