摘要
Background:Bladder cancer is the 10th most common cancer globally.The majority of bladder cancers are urothelial carcinomas(UCs),which,if locally advanced or metastatic,carry poor long-term prognosis.Cancer cells can evade the immune system by expressing the programmed cell death ligand 1 protein(PD-L1).Programmed cell death ligand 1 protein binds to programmed cell death protein 1(PD-1)onT cells,inhibiting their antitumor action.Bladder tumor cells also overexpress nectin-4,a cell adhesion polypeptide that contributes to metastasis,worsening prognosis.Current platinum-based chemotherapy treatments are suboptimal.This review aimed to assess novel treatments for locally advanced or metastatic UC that specifically target PD-L1 or nectin-4,namely,the PD-1 inhibitor pembrolizumab and the anti-nectin-4 antibody-drug conjugate enfortumab vedotin(EV).Materials and methods:Relevant English-language peer-reviewed articles and conference abstracts from the last 5 years were identified through MEDLINE and EMBASE database searches.A narrative review was performed,with key results outlined below.Results:Pembrolizumab was demonstrated to be superior to chemotherapy as a second-line treatment for platinum-unresponsive participants in the KEYNOTE-045 trial,resulting in its Food and Drug Administration(FDA)approval.Enfortumab vedotin therapy resulted in superior outcomes compared with chemotherapy in the EV-301 trial,resulting in FDA approval for its use for patients with locally advanced or metastatic UC who had previously undergone treatment with platinum-based chemotherapy and PD-1/PD-L1 inhibitors.Positive preliminary results for pembrolizumab and EV combination therapy have led to FDA approval in patients with locally advanced or metastatic UC who are not eligible for platinum chemotherapy.Conclusions:Pembrolizumab and EV represent novel treatment options for patients with locally advanced or metastatic UC with documented superior outcomes and tolerability as compared with standard chemotherapy.
