Atezolizumab Demonstrates Activity, Tolerability in Urothelial Carcinoma

Atezolizumab may have durable activity and acceptable tolerability in patients with metastatic urothelial carcinoma who have few treatment options after failure of platinum-based chemotherapy, according to a study published in The Lancet.¹

Researchers led by Jonathan Rosenberg, MD, of the Memorial Sloan Kettering Cancer Center in New York, NY, conducted a multicenter, single-arm, two-cohort phase 2 trial of 310 patients with inoperable locally advanced or metastatic urothelial carcinoma whose disease had progressed after previous platinum-based chemotherapy and received intravenous 1200 mg atezolizumab every 3 weeks.

Primary endpoint was an independent review facility-assessed objective response rate according to Response Evaluation in Criteria in Solid Tumors version 1.1 (RECIST v1.1).

PD-L1 expression status on infiltrating immune cells in the tumor microenvironment was defined by the percentage of PD-L1-positive immune cells IC0, IC1, and IC2. The researchers found that treatment with atezolizumab resulted in a significantly improved RECIST v1.1 objective response rate for each immune cell group as well as in all patients.

Upon exploratory analyses, The Cancer Genome Atlas (TCGA) subtypes and mutation load were found to be independently predictive for response to atezolizumab.

“This report is the first to show the association of TCGA subtypes with response to immune checkpoint inhibition and to show the importance of mutation load as a biomarker of response to this class of agents in advanced urothelial carcinoma,” the authors concluded.

Reference

1. Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial [published online ahead of print March 4, 2016]. The Lancet. doi: 10.1016/S0140-6736(16)00561-4.