High amounts of PD-L1 (programmed death ligand-1) expression may impact treatment decisions when treating locally advanced or metastatic urothelial bladder cancer (UBC).
High amounts of PD-L1 (programmed death ligand-1) expression may impact treatment decisions when treating locally advanced or metastatic urothelial bladder cancer (UBC). A new study (IMvigor 210) has found that experimental monoclonal antibody atezolizumab may be able to reduce tumor size in patients who have high levels of PD-L1 expression.
Atezolizumab (MPDL3280A, anti-PD-L1) is an investigational monoclonal antibody designed to target PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, preventing it from binding to PD-1 and B7-1 on the surface of T-cells.
The study showed atezolizumab shrank tumors in patients with locally advanced or metastatic UBC who had progressed on initial treatment (second-line or later). The researchers found that high amounts of PD-L1 expression by a patient’s cancer correlated with increased response to the medicine.
"We are encouraged by the number of people who responded to atezolizumab and maintained their response during the study because minimal progress has been made in advanced bladder cancer for nearly 30 years," said Sandra Horning, MD, who is the chief medical officer and head of Global Product Development for Genentech in San Francisco. "We plan to present results at an upcoming medical meeting, and will discuss next steps with health authorities to bring a new treatment option to patients as soon as possible."1
Dr. Horning said adverse events were consistent with what has been previously observed for atezolizumab. The US Food and Drug Administration (FDA) granted Breakthrough Therapy Designation in 2014 for atezolizumab in patients whose metastatic bladder cancer expresses PD-L1.
IMvigor 210 is an ongoing, open-label, multicenter, single-arm phase II study that is evaluating the safety and efficacy of atezolizumab in patients with locally advanced or metastatic UBC, regardless of PD-L1 expression. There are two cohorts in this trial. Cohort 1 consists of patients who have received no prior therapies for locally advanced or metastatic UBC, but who were ineligible for first-line cisplatin-based therapy. The results for this cohort are not yet mature. Cohort 2, for which results were announced July 12, 2015, included patients whose disease progressed during or following previous treatment with a platinum-based chemotherapy regimen (second-line or later).
In this study, patients received a 1200 mg intravenous dose of atezolizumab on day one of 21-day cycles until disease progression (Cohort 1) or loss of clinical benefit (Cohort 2). The primary endpoint of the study was objective response rate (ORR), and the secondary endpoints included duration of response, overall survival (OS), progression-free survival (PFS), and safety.
In addition to the IMvigor 210, Genentech has an ongoing randomized phase III study (IMvigor 211) comparing atezolizumab with standard of care chemotherapy in patients who have relapsed UBC. Currently, there are 11 ongoing or planned phase III studies of atezolizumab across certain kinds of lung, kidney, breast, and bladder cancers.