scholarly journals Immunotherapy in urothelial cancer: recent data and perspectives

2018 ◽  
Vol 13 (4) ◽  
pp. 16-24 ◽  
Author(s):  
M. I. Volkova ◽  
Ya. V. Gridneva ◽  
A. S. Ol’shanskaya
Keyword(s):  
Urothelial Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Standard Of Care ◽  
Phase Iii ◽  
Significant Survival ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Advanced Urothelial Carcinoma

Immune-checkpoint inhibitors blocking the programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyteassociated protein 4 (CTLA-4) have shown a prominent anti-tumor activity with long-term responses and an acceptable toxicity profile  in clinical trials. Pembrolizumab, atezolizumab, nivolumab, avelumab, and durvalumab are anti-PD-1/PD-L1 agents that redefine the standard of care for advanced urothelial carcinoma. CTLA-4 inhibitors are also under investigation in this setting. Phase III trial KEYNOTE-045 has demonstrated significant survival benefit in patients treated with pembrolizumab comparing with the standard second-line chemotherapy. Atezolizumab, nivolumab, avelumab, and durvalumab were also recommended for platinum-pretreated urothelial carcinoma patients based on phase II data. Following investigations of biomarkers such as PD-L1 expression are needed to determine high-responders to immunotherapy. This review article describes the advances in immunotherapy with immune-checkpoint inhibitors.

scholarly journals Prognostic and Predictive Factors in Advanced Urothelial Carcinoma Treated with Immune Checkpoint Inhibitors: A Review of the Current Evidence

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5517
Author(s):  
Sara Elena Rebuzzi ◽  
Giuseppe Luigi Banna ◽  
Veronica Murianni ◽  
Alessandra Damassi ◽  
Emilio Francesco Giunta ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Unmet Need ◽  
Predictive Biomarkers ◽  
Standard Of Care ◽  
Current Evidence ◽  
Concomitant Medications ◽  
Advanced Urothelial Carcinoma

In recent years, the treatment landscape of urothelial carcinoma has significantly changed due to the introduction of immune checkpoint inhibitors (ICIs), which are the standard of care for second-line treatment and first-line platinum-ineligible patients with advanced disease. Despite the overall survival improvement, only a minority of patients benefit from this immunotherapy. Therefore, there is an unmet need to identify prognostic and predictive biomarkers or models to select patients who will benefit from ICIs, especially in view of novel therapeutic agents. This review describes the prognostic and predictive role, and clinical readiness, of clinical and tumour factors, including new molecular classes, tumour mutational burden, mutational signatures, circulating tumour DNA, programmed death-ligand 1, inflammatory indices and clinical characteristics for patients with urothelial cancer treated with ICIs. A classification of these factors according to the levels of evidence and grades of recommendation currently indicates both a prognostic and predictive value for ctDNA and a prognostic relevance only for concomitant medications and patients’ characteristics.

scholarly journals First-Line Chemotherapy Response Is a Predictive Factor for Immune Checkpoint Inhibitors Treatment in Advanced Urothelial Carcinoma, a Real World Retrospective Study

2021 ◽  
Author(s):  
Jian-Ri Li ◽  
Shian-Shiang Wang ◽  
Kevin Lu ◽  
Chuan-Shu Chen ◽  
Chen-Li Cheng ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Urothelial Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
The Other ◽  
Chemotherapy Response ◽  
First Line ◽  
Advanced Urothelial Carcinoma ◽  
Line Chemotherapy

Abstract Background: Immune checkpoint inhibitors (ICIs) have become important tools for the treatment of advanced urothelial carcinoma (aUC). However, the clinical strategy using ICIs and chemotherapy is still controversy. The aim of this study was to evaluate the association of clinical parameters in aUC patients with ICIs treatment.Methods: We retrospectively analyzed aUC patients who received atezolizumab and pembrolizumab between January 2015 and October 2020. The associations between baseline demographics and clinical outcomes were evaluated.Results: Of the 74 included patients, the median age was 67 years. Among them, 53 patients received atezolizumab and the other 21 received pembrolizumab. There were 50 patients receiving first line ICIs therapy and the other 24 received second line monotherapy. Fifty-two (83.87%, 52/62) received cisplatin among all chemotherapy patients. The median progression free survival was 10.94 months and the overall survival was 28.44 months. Poor chemotherapy response or no chemotherapy, liver metastases, Eastern Cooperative Oncology Group (ECOG) status and higher neutrophil/lymphocyte ratio (NLR) were associated with higher risk of diseases progression (HR=5.70, 95% CI 2.04-15.90, p=0.001, HR=6.08, 95% CI 1.79-20.57, p=0.004; HR=5.40, 95% CI 1.76-16.57, p=0.003; HR=6.08, 95% CI 2.56-14.44, p<0.001 and HR= 1.02, 95% CI 1.01-1.03, P=0.002 respectively). Liver metastases and WBC before ICI were associated with increased death risk (HR=11.95, 95%CI 3.22-44.34, p<0.001; HR=1.0001, 95% CI 1.00001-1.00002, p=0.036 respectively) while ICI response was associated with decreased death (HR=0.22, 95%CI 0.08-0.62, p=0.004). Chemotherapy responders were associated with better ICI treatment response (OR=6.52, 95%CI 1.45-29.24, p=0.014) while lymph node metastases and poor ECOG was associated with poor ICI response (OR=0.31, 95%CI 0.10-0.94, p=0.038; OR=0.32, 95%CI 0.11-0.95, p=0.040).Conclusions: Our data showed predictive role of first-line chemotherapy response to ICIs treatment efficacy in aUC patients as well as other prognostic factors, such as ECOG status, serum white blood cell count or NLR and liver metastases.

scholarly journals Immune Checkpoint Inhibitors for Brain Metastases: A Primer for Neurosurgeons

Neurosurgery ◽  
2020 ◽  
Vol 87 (3) ◽  
pp. E281-E288
Author(s):  
Elisa Aquilanti ◽  
Priscilla K Brastianos
Keyword(s):  
Brain Metastases ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Standard Of Care ◽  
Nonsmall Cell Lung Cancer ◽  
Immune Recognition ◽  
Therapeutic Modalities ◽  
Programmed Death 1

Abstract Immune checkpoint inhibitors enhance immune recognition of tumors by interfering with the cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) and programmed death 1 (PD1) pathways. In the past decade, these agents brought significant improvements to the prognostic outlook of patients with metastatic cancers. Recent data from retrospective analyses and a few prospective studies suggest that checkpoint inhibitors have activity against brain metastases from melanoma and nonsmall cell lung cancer, as single agents or in combination with radiotherapy. Some studies reported intracranial response rates that were comparable with systemic ones. In this review, we provide a comprehensive summary of clinical data supporting the use of anti-CTLA4 and anti-PD1 agents in brain metastases. We also touch upon specific considerations on the assessment of intracranial responses in patients and immunotherapy-specific toxicities. We conclude that a subset of patients with brain metastases benefit from the addition of checkpoint inhibitors to standard of care therapeutic modalities, including radiotherapy and surgery.

scholarly journals Pembrolizumab in the treatment of locally advanced or metastatic urothelial carcinoma: clinical trial evidence and experience

2019 ◽  
Vol 11 ◽  
pp. 175628721983928 ◽  
Author(s):  
Michael Crist ◽  
Gopa Iyer ◽  
Miles Hsu ◽  
William C. Huang ◽  
Arjun V. Balar
Keyword(s):  
Urothelial Carcinoma ◽  
Clinical Efficacy ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Inhibitory Interaction ◽  
Combination Strategies ◽  
Clinical Trial Evidence ◽  
Advanced Urothelial Carcinoma

The treatment of advanced urothelial carcinoma (UC) has dramatically changed with the advent of immune checkpoint inhibitors that disrupt the T-cell inhibitory interaction between the programmed cell death (PD)-1 receptor and its ligand (PD-L1). Pembrolizumab, a highly specific, monoclonal antibody directed against PD-1, has demonstrated clinical efficacy as well as a favorable toxicity profile, and has emerged as a new standard of care in the treatment of advanced UC. This review will summarize clinical efficacy from recent trials that led to the approval of pembrolizumab in treating platinum-refractory advanced UC as well as treating patients who are ineligible for first-line cisplatin-containing chemotherapy. While immune checkpoint inhibition has reinvigorated the treatment landscape of advanced UC and generated a great deal of optimism, only a minority of patients benefit. Combination strategies with the goal of increasing response rates are desperately needed as are biomarkers predictive of response.

scholarly journals Disparities in the Use of Programmed Death 1 Immune Checkpoint Inhibitors

2018 ◽  
Vol 23 (11) ◽  
pp. 1388-1390 ◽  
Author(s):  
Jeremy M. O'Connor ◽  
Kathi Seidl‐Rathkopf ◽  
Aracelis Z. Torres ◽  
Paul You ◽  
Kenneth R. Carson ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Programmed Death ◽  
Programmed Death 1

scholarly journals Immune checkpoint inhibitors in renal cell carcinoma

2017 ◽  
Vol 131 (21) ◽  
pp. 2627-2642 ◽  
Author(s):  
Kirsty Ross ◽  
Rob J. Jones
Keyword(s):  
Renal Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Critical Role ◽  
Optimal Timing ◽  
New Class ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Immune Manipulation

The immune system has long been known to play a critical role in the body’s defence against cancer, and there have been multiple attempts to harness it for therapeutic gain. Renal cancer was, historically, one of a small number of tumour types where immune manipulation had been shown to be effective. The current generation of immune checkpoint inhibitors are rapidly entering into routine clinical practice in the management of a number of tumour types, including renal cancer, where one drug, nivolumab, an anti-programmed death-1 (PD-1) monoclonal antibody (mAb), is licensed for patients who have progressed on prior systemic treatment. Ongoing trials aim to maximize the benefits that can be gained from this new class of drug by exploring optimal timing in the natural course of the disease as well as combinations with other checkpoint inhibitors and drugs from different classes.

PD-L1 SNPs as biomarkers to define benefit in patients with advanced NSCLC treated with immune checkpoint inhibitors

2021 ◽  
pp. 030089162110149
Author(s):  
Roberta Minari ◽  
Francesco Bonatti ◽  
Giulia Mazzaschi ◽  
Alessandra Dodi ◽  
Francesco Facchinetti ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Immune Checkpoint ◽  
Clinical Benefit ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Nucleotide Polymorphisms ◽  
Entire Cohort ◽  
Programmed Death ◽  
Programmed Death 1

Objective: To investigate the role of CTLA-4, PD-1 (programmed death-1), and PD-L1 (programmed death-ligand 1) single nucleotide polymorphisms (SNPs) in predicting clinical outcome of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). Methods: A total of 166 consecutive patients were included. We correlated SNPs with clinical benefit, progression-free survival, time to treatment failure, and overall survival and evaluated the incidence of SNPs in nonresponder and long clinical benefit groups. Results: Considering the entire cohort, no correlation was found between SNPs and clinical outcome; however, PD-L1 rs4143815 SNP and the long clinical benefit group showed a statistically significant association ( p = 0.02). The nonresponder cohort displayed distinctive PD-L1 haplotype ( p = 0.05). Conclusion: PD-L1 SNPs seem to be marginally involved in predicting clinical outcome of NSCLC treated with ICI, but further investigations are required.

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