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.

Urothelial carcinoma in the era of immune checkpoint inhibitors

Immunotherapy ◽  
2021 ◽  
Author(s):  
Nadine Khalife ◽  
Claude Chahine ◽  
Manal Kordahi ◽  
Tony Felefly ◽  
Hampig Raphael Kourie ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Urothelial Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Invasive Disease ◽  
Line Treatment ◽  
First Line ◽  
Metastatic Urothelial Carcinoma ◽  
Muscle Invasive

Bladder cancer is the seventh most frequent cancer worldwide. The majority of patients present with nonmuscle invasive disease, while 20% of the patients are diagnosed with muscle-invasive bladder cancer. The treatment of nonmuscle invasive disease is endoscopic resection followed by intravesical adjuvant treatment for high risk patients. The standard treatment of localized muscle-invasive disease is neoadjuvant chemotherapy followed by radical cystectomy. Platinum-based chemotherapy is the first-line treatment in locally advanced or metastatic urothelial carcinoma. Immune checkpoint inhibitors have been approved for the treatment of metastatic urothelial carcinoma as second-line treatment or first-line in platinum-ineligible patients. Recently, pembrolizumab have been approved in BCG-refractory nonmuscle invasive bladder cancer. This review summarizes the current evidence concerning immunotherapy in the treatment of urothelial carcinoma.

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 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.

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