Emerging Role of Immunotherapy in Advanced Urothelial Carcinoma
Purpose of Review
Advanced urothelial carcinoma (aUC) has long been treated preferably with cisplatin-based chemotherapy, but many patients are cisplatin-ineligible whereas for those who progress on a platinum-based regimen treatment options are limited. We review key recent data regarding immune checkpoint inhibitors that are changing this treatment landscape.
Since May 2016, five different agents targeting the PD-1/PD-L1 pathway (atezolizumab, pembrolizumab, nivolumab, avelumab, durvalumab) have received FDA approval for the treatment of aUC in the platinum-refractory setting, while pembrolizumab and atezolizumab are FDA-approved for cisplatin-ineligible patients in the first-line setting. Clinical outcomes and safety profiles of these agents appear relatively comparable across separate trials; however, only pembrolizumab is supported by level I evidence from a large randomized phase III trial showing overall survival benefit over conventional cytotoxic salvage chemotherapy in the platinum-refractory setting.
Pembrolizumab has the highest level of evidence in platinum-refractory aUC, whereas pembrolizumab and atezolizumab have comparable level of evidence in the frontline setting in cisplatin-ineligible patients. Ongoing research is evaluating novel agents, various rational combinations, and sequences, as well as predictive and prognostic biomarkers.
KeywordsMetastatic bladder cancer Advanced urothelial carcinoma Immunotherapy Immune checkpoint inhibitors PD-1 PD-L1 Cisplatin-ineligible Platinum-refractory Atezolizumab Pembrolizumab Avelumab Nivolumab Durvalumab Biomarkers clinical trials
Compliance with Ethical Standards
Conflict of Interest
Vadim S. Koshkin declares that he has no conflict of interest.
Petros Grivas has received compensation from Genentech, Dendreon, Bayer, Merck, Bristol-Myers Squibb, Exelixis, AstraZeneca, Biocept, Clovis Oncology, and EMD Serono for service as a consultant; participated in educational, unbranded, not product-related speaker’s program (after providing direct input for slides content) for Genentech and Bristol-Myers Squibb; and received support for conduction of clinical trials (to Cleveland Clinic Foundation) from Genentech, Bayer, Merck, Mirati, Oncogenex, Pfizer, Bristol-Myers Squibb, and AstraZeneca.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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