Abstract
Metastatic urothelial cancer is an aggressive disease associated with a poor prognosis. In the first-line setting, platinum-based chemotherapy is the standard of care but resistance rapidly occurs. After failure of platinum-based therapy and in cisplatin-ineligible patients, therapeutic options are limited. Malignant cells evolve mechanisms to evade immune recognition, including the expression of cell-surface molecules, named immune checkpoints, on tumor and tumor-specific lymphocytes. Immunotherapy, by targeting these checkpoints, represents a new tool to improve the patient outcome in advanced urothelial carcinoma (UC). Recently, the US FDA approved, in a short time, several immune checkpoint inhibitors in metastatic UC, both after failure of platinum-based therapy and in first-line setting in cisplatin-ineligible patients. This article aims to review the place of immunotherapy in advanced UC.
Highlights
The Phase II NCT02553642 is currently ongoing to evaluate the relationship between TMB and predicted neoantigen burden and response to nivolumab/ipilimumab in advanced BC
Immunotherapy is becoming a standard of care in metastatic urothelial carcinoma, improving survival outcome of patients
Pembrolizumab has a level 1 evidence in this setting as it was confirmed in a randomized Phase III clinical trial
Summary
Survival results were better than those observed with historical second-line agents such as vinflunine, ifosfamide or paclitaxel [7,8,9]. About 16% of patients experienced Grade 3/4 TRAEs, including 5% of immune-related AEs, reflecting a better toxicity profile compared with chemotherapy [17] These promising results led to the randomized Phase III IMvigor211 trial that compared atezolizumab with standard second-line chemotherapy (vinflunine, paclitaxel, docetaxel) in 931 mUC patients after failure of platinum-based chemotherapy. Consistently with Imvigor210 results, the median DOR with atezolizumab was 21.7 months in the overall study population, compared with 7.4 months with chemotherapy, confirming robust antitumoral efficacy of atezolizumab [18] In light of these results and the better safety profile compared with chemotherapy, atezolizumab appears to be an alternative to chemotherapy in second-line metastatic setting in mUC, the absence of level 1. Grade 3/4 TRAEs occurred in 6.8%, including 2% Grade 3/4 immune-mediated AEs. The median PFS was 1.5 months in the entire population and was higher in PD-L1 high patients (2.1 months) compared with low or negative patients (1.4 months). Selection of patients appears very important when initiating future science group www.future-science.com
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