In the IMvigor 210 study, the investigational cancer immunotherapy Atezolizumab ( MPDL3280A; anti-PD-L1 ) shrank tumors ( objective response rate; ORR; the primary end point of this study ) in people with locally advanced or metastatic urothelial bladder cancer who had progressed on initial treatment ( second-line or later ).
High amounts of PD-L1 ( Programmed Death Ligand-1 ) expression by a person’s cancer correlated with increased response to the medicine.
Adverse events were consistent with what has been previously observed for Atezolizumab.
In 2014, the FDA ( Food and Drug Administration ) granted Breakthrough Therapy Designation for Atezolizumab in people whose metastatic bladder cancer expresses PD-L1.
This designation is designed to expedite the development and review of medicines intended to treat serious diseases.
IMvigor 210 is an open-label, multicenter, single-arm phase II study that evaluated the safety and efficacy of Atezolizumab in people with locally advanced or metastatic urothelial bladder cancer, regardless of PD-L1 expression.
People in the study were enrolled into one of two cohorts. Cohort 1 consisted of people who had received no prior therapies for locally advanced or metastatic urothelial bladder cancer, but who were ineligible for first-line Cisplatin-based therapy; results for this cohort are not yet mature. Cohort 2 included people whose disease progressed during or following previous treatment with a Platinum-based chemotherapy regimen ( second-line or later ).
People received a 1200-milligram intravenous dose of Atezolizumab on day one of 21-day cycles until progressive disease ( Cohort 1 ) or loss of clinical benefit ( Cohort 2 ).
The primary endpoint of the study was ORR. Secondary endpoints included duration of response, overall survival, progression-free survival and safety.
PD-L1 expression was assessed using an investigational immunohistochemistry test being developed by Roche Diagnostics.
In addition to the IMvigor 210, a phase III study, IMvigor 211, is ongoing. This trial compares Atezolizumab with standard-of-care chemotherapy in people who have relapsed urothelial bladder cancer.
Atezolizumab is a monoclonal antibody designed to interfere with a protein called PD-L1. Atezolizumab is 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. By inhibiting PD-L1, Atezolizumab may enable the activation of T cells.
All studies of Atezolizumab include the evaluation of an investigational IHC test that uses the antibody SP142 to measure PD-L1 expression on both tumor cells and infiltrating immune cells. The goal of PD-L1 as a biomarker is to identify those people most likely to benefit when treated with Atezolizumab alone, and to determine which people may benefit most from a combination of Atezolizumab and another medicine.
Metastatic urothelial bladder cancer is associated with a poor prognosis and limited treatment options. According to the American Cancer Society ( ACS ), it is estimated that more than 74,000 Americans will be diagnosed with bladder cancer in 2015, and approximately 15,000 of new diagnoses are made when bladder cancer is in advanced stages. There is a dramatic difference in survival rates between early and advanced bladder cancer.
The ACS estimates that approximately 15% of people with advanced bladder cancer ( stage IV ) will live for five years, compared to 88% when diagnosed during stage I.
Men are about three to four times more likely to get bladder cancer during their lifetime than women. ( Xagena )
Source: Genentech, 2015