Checkpoint inhibitors in the treatment of urological malignancies

Popović, Lazar; Matovina-Brko, Gorana; Popović, Maja

doi:10.1136/esmoopen-2017-000165

Cited by 23 publications

(12 citation statements)

References 57 publications

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“…The success of BCG in treating NMIBC has emphasized BC as an immune sensitive disease, and the role of immune checkpoints inhibitors like pembrolizumab is also being researched in NMIBC patients, relapsing after the BCG treatment (KEYNOTE-057) 51. Inman et al reported that PD-L1 tumor cell expression was associated with increased resistance to BCG therapy, which suggests that TCs might be protected from attack by ICs through immune checkpoints, since a fully functional immune system is prerequisite for BCG efficacy 52.…”

Section: Discussionmentioning

confidence: 99%

<p>Clinicopathological and prognostic value of PD-L1 in urothelial carcinoma: a meta-analysis</p>

Ding¹,

Chen²,

Yang³

et al. 2019

CMAR

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Objective: Our objective was to conduct a meta-analysis to investigate the clinicopathological features and prognostic value of programmed cell death ligand 1 (PD-L1) expression in patients with urothelial carcinoma (UC). Materials and methods: Twenty-seven studies with 4,032 patients were included in the meta-analysis. Pooled ORs and 95% CIs were used to examine the associations between clinical factors and PD-L1 expression. HRs and 95% CIs were extracted from eligible studies. Heterogeneity was evaluated using the chi-squared-based Q test and I 2 statistic. Results: Expression of PD-L1 on tumor cells (TCs) was associated with muscle-invasive disease (OR=3.67, 95% CI: 2.53–5.33), and inversely associated with the history of intravesical bacilli Calmette-Guerin therapy (OR=0.39, 95% CI: 0.18–0.82) in bladder cancer patients. PD-L1 expression on TCs was associated with worse overall survival (HR=2.06, 95% CI: 1.38–3.06) in patients with organ-confined bladder cancer. PD-L1 expression in patients with UC was significantly related to better objective response rate after PD-1/PD-L1 antibody treatment. Conclusions: Expression of PD-L1 on TCs was associated with muscle-invasive disease in patients with bladder cancer. Patients with PD-L1-positive UC had a significantly better response to PD-1/PD-L1 targeted treatment.

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Section: Discussionmentioning

confidence: 99%

<p>Clinicopathological and prognostic value of PD-L1 in urothelial carcinoma: a meta-analysis</p>

Ding¹,

Chen²,

Yang³

et al. 2019

CMAR

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“…The therapeutic synergy of the combination of EBRT (external beam radiation therapy) and iplimumab (monoclonal anti-CTLA-4 antibody) has also been confirmed [4,7,31,41]. A phase III trial in patients with mCRPC who had progressed after docetaxel chemotherapy, compared iplimumab in combination with palliative radiotherapy for bone metastases to radiotherapy alone.…”

Section: Impact Of Monoclonal Antibodies Directed Against Immune Checmentioning

confidence: 98%

The role of immune checkpoint inhibitors in prostate cancer

Surdacki¹,

Szudy‐Szczyrek

Gorący

et al. 2019

Ann Agric Environ Med.

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Introduction. Prostate cancer (PC) is the most commonly diagnosed malignant tumour and the third cause of cancer deaths among men in Europe. The treatment of early-stage PC is very effective and in many cases allows achievement of a complete cure, whereas the treatment of metastatic prostate cancer (mPC) is still a huge challenge for clinicians. New therapeutic strategies for mPC are urgently needded. One of the most promising methods of treatment is anticancer immunotherapy including the monoclonal antibodies against immune checkpoint inhibitors. Objectives. To present the potential possibilities of using checkpoint inhibitors blockage in the treatment of mPC, and to overview the results of recent research on immune checkpoint inhibitors in patients with PC. State of knowledge. Recent studies suggest that monoclonal antibodies directed against immune checkpoint inhibitors in combination with traditional therapy may become a breakthrough in the treatment of mPC in the near future. Conclusions. The immunotherapy using monoclonal antibodies against immune checkpoint inhibitors seems to be a new opportunity for patients with advanced PC. The key to achieve the maximum anti-tumour response is to choose the best candidates for this therapy and determine the optimal sequence and combination of drugs. The introduction of immunotherapy as the standard treatment of patients with advanced PC requires further studies.

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“…Recently, immune checkpoint blockade monoclonal antibodies (moAbs) have been demonstrated to be effective for RCC and BC. However, the efficacy is in the range of 20–40% . New therapeutic modalities are needed for patients with refractory disease.…”

mentioning

confidence: 99%

Vaccination of Urological Cancer Patients With WT1 Peptide‐Pulsed Dendritic Cells in Combination With Molecular Targeted Therapy or Conventional Chemotherapy Induces Immunological and Clinical Responses

2018

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The prognosis of metastatic or relapsed renal cell carcinoma (RCC) or bladder cancer (BC) remains poor despite the introduction of immune checkpoint blockade agents. We aimed to investigate the safety and the feasibility of a vaccination with WT1 peptide-loaded dendritic cells (DCs) and OK-432 adjuvant combined with molecular targeted therapy or conventional chemotherapy. Five eligible patients with metastatic or relapsed RCC and five eligible patients with BC were enrolled. No severe adverse events related to a vaccination were observed. Seven patients with RCC or non-muscle invasive BC had durable stable disease and three other patients had disease progression after DC vaccination. DC vaccination augmented WT1 specific immunity and the reduction of regulatory T cells which might be related to clinical outcome. These results indicate that DC-based immunotherapy combined with a molecular targeted therapy or a conventional chemotherapy is safe and feasible for patients in advanced stage of RCC or BC.

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Checkpoint inhibitors in the treatment of urological malignancies

Cited by 23 publications

References 57 publications

<p>Clinicopathological and prognostic value of PD-L1 in urothelial carcinoma: a meta-analysis</p>

<p>Clinicopathological and prognostic value of PD-L1 in urothelial carcinoma: a meta-analysis</p>

The role of immune checkpoint inhibitors in prostate cancer

Vaccination of Urological Cancer Patients With WT1 Peptide‐Pulsed Dendritic Cells in Combination With Molecular Targeted Therapy or Conventional Chemotherapy Induces Immunological and Clinical Responses

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