Recent approvals by the US Food and Drug Administration (FDA) and ongoing clinical trials of immunotherapies for metastatic bladder cancer enabled improvements in clinical care for the first time in decades. In 2016, for example, the PD-L1 inhibitor atezolizumab was approved for metastatic urothelial carcinoma (mUC), followed in 2017 by the approval of the PD-1 inhibitor, nivolumab, for the same indication.
“Evidence that inhibition of the PD-1/PD-L1 pathway has clinical activity in patients with mUC opened the door to the investigation of additional immune therapies, either as single agents or in combination with a broad array of agents, in an effort to increase the number of patients who respond to T cell checkpoint blockade,” explained the authors of a recent review published in Current Opinion in Oncology.1
Around a third of patients with urothelial carcinoma present with muscle-invasive disease (T2-T4a), a staging with poor prognosis likely due to occult metastases. Metastatic disease is incurable and is treated with cisplatin-based combination systemic therapy, though many patients are ineligible for this treatment due to renal insufficiency.
PD-1 and PD-L1 checkpoint inhibitors have, however, yielded durable clinical responses in subgroups of previously treated and treatment-naïve patients with mUC.
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Immunotherapy combinations such as PD-1 inhibition and cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibition (eg ipilimumab) also show promising results in improved response rates in urothelial carcinoma.