William Tabayoyong1, Jianjun Gao2. 1. The University of Texas MD Anderson Cancer Center, Department of Urology. 2. The University of Texas MD Anderson Cancer Center, Department of Genitourinary Medical Oncology, Houston, Texas, USA.
Abstract
PURPOSE OF REVIEW: Recent Food and Drug Administration (FDA) approval of five new immune checkpoint inhibitors for the treatment of metastatic urothelial cancer represents the first major treatment breakthrough for this disease since the introduction of combination chemotherapy over 30 years ago. This review examines the recent clinical trials leading to FDA approval of these agents, the current challenges facing immunotherapy and areas that require further research. RECENT FINDINGS: The programmed death 1 receptor (PD-1) and its ligand programmed death ligand-1 (PD-L1) are important negative regulators of immune activity, preventing destruction of normal tissues and autoimmunity. Aggressive bladder cancer cells express aberrantly high levels of PD-L1, hijacking the normal immune-regulatory pathway to evade detection and destruction by the immune system. Blockade of the PD-1/PD-L1 axis with immune checkpoint inhibitors augments the immune system's ability to eradicate bladder cancer with impressive safety and tolerability profiles. SUMMARY: Recent clinical trials demonstrate that patients with metastatic urothelial carcinoma are responsive to immune checkpoint inhibitor therapy. Optimal treatment regimens are still under development, but activity has been demonstrated in both the first and second-line setting for metastatic disease.
PURPOSE OF REVIEW: Recent Food and Drug Administration (FDA) approval of five new immune checkpoint inhibitors for the treatment of metastatic urothelial cancer represents the first major treatment breakthrough for this disease since the introduction of combination chemotherapy over 30 years ago. This review examines the recent clinical trials leading to FDA approval of these agents, the current challenges facing immunotherapy and areas that require further research. RECENT FINDINGS: The programmed death 1 receptor (PD-1) and its ligand programmed death ligand-1 (PD-L1) are important negative regulators of immune activity, preventing destruction of normal tissues and autoimmunity. Aggressive bladder cancer cells express aberrantly high levels of PD-L1, hijacking the normal immune-regulatory pathway to evade detection and destruction by the immune system. Blockade of the PD-1/PD-L1 axis with immune checkpoint inhibitors augments the immune system's ability to eradicate bladder cancer with impressive safety and tolerability profiles. SUMMARY: Recent clinical trials demonstrate that patients with metastatic urothelial carcinoma are responsive to immune checkpoint inhibitor therapy. Optimal treatment regimens are still under development, but activity has been demonstrated in both the first and second-line setting for metastatic disease.
Authors: Deborah Blythe Doroshow; Sheena Bhalla; Mary Beth Beasley; Lynette M Sholl; Keith M Kerr; Sacha Gnjatic; Ignacio I Wistuba; David L Rimm; Ming Sound Tsao; Fred R Hirsch Journal: Nat Rev Clin Oncol Date: 2021-02-12 Impact factor: 66.675