Atezolizumab in patients with renal insufficiency and mixed variant histology: analyses from an expanded access program in platinum-treated locally advanced or metastatic urothelial carcinoma.

Atezolizumab is a treatment for locally advanced/metastatic urothelial carcinoma (mUC). However, its use in patients with renal insufficiency or UC with mixed variant histology (MVH) is not well characterized.

To report efficacy and safety of atezolizumab in these special subpopulations from an expanded access program (EAP).

A total of 218 patients were enrolled at 36 US study sites (November 2015-August 2016), and the trial ended following the approval of atezolizumab by the US Food and Drug Administration. This post hoc analysis investigated outcomes in specific study subgroups.

Atezolizumab 1200 mg was administered intravenously every 3 weeks until loss of clinical benefit, unacceptable toxicity, death, consent withdrawal, decision to discontinue, commercial availability, or study closure.

Response Evaluation Criteria in Solid Tumors V.1.1 responses and safety were evaluated by baseline renal function and histology.

Objective responses occurred in 0/6 (0%), 4/19 (21%), 1/27 (3.7%), and 12/62 (19%) of evaluable patients with creatinine clearance (CrCl) <30, 30-45, 45-60, and ≥60 mL/min, respectively, and stable disease was seen in three patients with CrCl <30 mL/min. Objective responses were seen in 13/102 patients (13%) with urothelial carcinoma (UC) histology only and in 4/12 patients (33%) with UC with MVH. Treatment-related adverse event frequencies ranged from 35% to 54% across the earlier indicated CrCl subgroups and they were also similar in patients with pure UC or UC with MVH (46%).

In this EAP mUC subgroup analysis, clinical benefit of atezolizumab occurred in patients with compromised renal function or MVH UC tumors. Safety was comparable across subgroups.

We examined the efficacy and safety of atezolizumab for UC in certain patients participating in an EAP. We found that responses to atezolizumab occurred, and safety was similar, in most patient subgroups with varying levels of kidney functioning or less common types of tumor tissue histology.

Journal for immunotherapy of cancer. 2020 Jul [Epub]

Jean Hoffman-Censits, Sumanta Pal, Constanze Kaiser, Beiying Ding, Joaquim Bellmunt

Departments of Oncology and Urology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA, Baltimore, Maryland, USA ., Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, California, USA., Genentech Inc, South San Francisco, California, USA., Director, Bladder Cancer Program, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.