Atezolizumab: A PD-L1–Blocking Antibody for Bladder Cancer

• Published in: Clinical cancer research Vol. 23; no. 8; pp. 1886 - 1890
• Main Authors: Inman, Brant A., Longo, Thomas A., Ramalingam, Sundhar, Harrison, Michael R.
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research Inc 15.04.2017
• Subjects: Antibodies, Monoclonal - therapeutic use; Antineoplastic Agents - therapeutic use; B7 antigen; B7-H1 Antigen - antagonists & inhibitors; Binding; Bladder; Bladder cancer; Blocking antibodies; Cancer; Carcinoma, Transitional Cell - drug therapy; Chemotherapy; Cisplatin; Clinical trials; Humans; Immune checkpoint; Immunity; Immunoglobulin G; Immunosuppression; Immunotherapy; Leukocytes; Lymphocytes T; Metastases; Metastasis; Monoclonal antibodies; Patients; PD-1 protein; PD-L1 protein; Platinum; Receptors; Response rates; Survival; Targeted cancer therapy; Toxicity; Tumors; Urinary bladder; Urinary Bladder Neoplasms - drug therapy
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-16-1417

Atezolizumab (Tecentriq, MPDL3280A; Genentech/Roche) is an FcγR binding–deficient, fully humanized IgG1 mAb designed to interfere with the binding of PD-L1 ligand to its two receptors, PD-1 and B7.1. By blocking the PD-L1/PD-1 immune checkpoint, atezolizumab reduces immunosuppressive signals found within the tumor microenvironment and, consequently, increases T-cell–mediated immunity against the tumor. Atezolizumab has been FDA approved as second-line therapy for advanced bladder cancer. This accelerated approval was based on phase II trial data in patients with metastatic bladder cancer that showed unexpected and durable tumor responses. In subjects whose tumors progressed on first-line platinum-based chemotherapy, the objective response rate was 15%, the complete response rate was 5%, and 1-year overall survival was 36%. In subjects that were chemotherapy naïve and cisplatin ineligible, the objective response rate was 24%, the complete response rate was 7%, and 1-year overall survival was 57%. Better responses were associated with higher PD-L1 expression on the tumor-infiltrating leukocytes. These data suggest that patients with advanced bladder cancer treated with atezolizumab have significantly better response rates and survival than historical controls treated with other second-line regimens. The toxicity profile of atezolizumab is also favorable. Trials are currently assessing whether atezolizumab is effective in earlier bladder cancer stages and in the first-line metastatic setting. Clin Cancer Res; 23(8); 1886–90. ©2016 AACR.