Atezolizumab: a PD-L1 blocking antibody for bladder cancer

Atezolizumab (Tecentriq™, MPDL3280A) is an FcR-binding deficient, fully humanized, IgG1 monoclonal antibody 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 microenvironement 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 2 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 favourable. Trials are currently assessing whether atezolizumab is effective in earlier bladder cancer stages and in the first line metastatic setting.

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