Recent advances in medical therapy for metastatic urothelial cancer

Abstract

Cytotoxic chemotherapy has been the mainstay of medical therapy for metastatic urothelial cancer. Currently, the gemcitabine/cisplatin regimen is widely used worldwide as the standard first-line medical treatment. Very recently, in 2017, pembrolizumab, a highly selective, humanized monoclonal IgG4κ isotype antibody against programmed death 1, was approved as a second-line treatment to be used after platina-based chemotherapy for metastatic urothelial cancer in Japan. Based on its promising anti-tumor efficacy and manageable safety profile as demonstrated in the phase III KEYNOTE-045 trial, pembrolizumab therapy is expected to be rapidly introduced for treating metastatic urothelial cancer in clinical practice. The paradigm of medical treatment for patients with metastatic UC is dramatically changing through the introduction of this and other immune-checkpoint inhibitors. In this article, we provide a brief overview of these immune-checkpoint inhibitors and a comprehensive summary of the use of cytotoxic chemotherapy for metastatic urothelial cancer, including ongoing clinical trials.

Keywords: Chemotherapy; GC regimen; Immune-checkpoint inhibitor; MVAC regimen; Pembrolizumab; Urothelial cancer.

Fig. 1

Anti-PD-1/PD-L1 novel immune therapy. When a complex of PD-L1 expressed by cancer cells engages PD-1 expressed on CD8-positive CTLs, immune tolerance is achieved. Destruction of this immune tolerance using immune-checkpoint inhibitors is the latest novel form of immune therapy. MHC major histocompatibility, CTL cytotoxic T lymphocytes, PD-1 programmed death-1, PD-L1 programmed death ligand 1, TCR T cell receptor