Patients with metastatic urothelial carcinoma have few established treatment options, and standard-of-care therapy typically prolongs survival by only 9–15 months. Now, findings of a phase II clinical trial indicate that a subset of these patients respond to the anti-programmed cell-death 1 ligand-1 (PD-L1) humanized monoclonal antibody atezolizumab.

In this single-arm trial, 315 patients with inoperable, advanced-stage or metastatic urothelial carcinoma, whose disease had progressed despite receiving previous platinum-based chemotherapy, were enrolled. The extent of pretreatment PD-L1 expression upon enrolment was determined using immunohistochemical analyses of tumour-infiltrating lymphocytes (TILs) in biopsy samples. Patients received 3-weekly doses of atezolizumab: 26% of patients with >5% PD-L1-positive TILs and 18% of those with >1% PD-L1-positive TILs had an objective response to treatment. Although no comparator arm was included, this value is substantially higher than the ∼10% of patients who respond to frequently used cytotoxic agents, as demonstrated by previous research.

At the time of publication, patients had a median response duration of 11.7 months, and 84% of patients had an ongoing response. Grade 3 or 4 treatment-related adverse events ocurred in 16% of patients, with grade 3 or 4 immune-related adverse events, including pneumonitis, rash and dyspnoea in 5%.

These findings indicate that atezolizumab provides a viable alternative to cytotoxic chemotherapies for patients with metastatic urothelial carcinoma, despite substantial pretreatment with other therapies, and is particularly effective in patients with elevated PD-L1 expression on TILs. Longer-term follow up data on the outcomes of patients who continue to respond to atezolizumab are eagerly awaited.

This article is modified from the original in Nat. Rev. Urol. (http://dx.doi.org/10.1038/nrurol.2016.60).