title: Pharmacokinetic drug evaluation of atezolizumab for the treatment of locally advanced or metastatic urothelial carcinoma.
abstract: Muscle invasive bladder cancer (MIBC) is difficult to manage for patients who progress during or after initial chemotherapy regimens. Current regimens offer low response rates with high toxicities. The advent of immune checkpoint inhibitors may represent a new opportunity for effective management of these patients. Areas covered: Atezolizumab is an engineered humanized monoclonal immunoglobulin G1 antibody that binds selectively to PD-L1 and prevents its interaction with PD-1 and B7-1. It is administered intravenously and is given every 3 weeks as long as there is no evidence of tumor progression. Phase I trials confirmed antitumor activity of atezolizumab in patients with advanced or metastatic urothelial carcinoma. Phase II trials showed an improved response rate and a longer durable response than current conventional therapy. Phase III trials are currently underway with an estimated accrual end date of 2017. Expert opinion: MIBC is a high-risk disease, and after progression on current chemotherapy regimens, second-line treatments leave much to be desired. Emerging evidence of efficacy and safety and a recent accelerated approval by the FDA presents atezolizumab as a promising treatment option. Current clinical challenges include the details of disease progression and determining where immune checkpoint inhibition will reside in the treatment algorithm.
authors.affiliation: a Division of Urology , Rutgers Robert Wood Johnson Medical School , New Brunswick , NJ , USA.
authors.forename: Rutveej
authors.initials: R
authors.lastname: Patel
authors.affiliation: a Division of Urology , Rutgers Robert Wood Johnson Medical School , New Brunswick , NJ , USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Bock
authors.affiliation: a Division of Urology , Rutgers Robert Wood Johnson Medical School , New Brunswick , NJ , USA.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Polotti
authors.affiliation: a Division of Urology , Rutgers Robert Wood Johnson Medical School , New Brunswick , NJ , USA.|b Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey , Rutgers Robert Wood Johnson Medical School , New Brunswick , NJ , USA.
authors.forename: Sammy
authors.initials: S
authors.lastname: Elsamra
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D060890:B7-H1 Antigen / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C000594389:atezolizumab
keywords: Atezolizumab; clinical efficacy; pharmacodynamics; pharmacokinetics; urothelial cancer