Atezolizumab in people with previously treated advanced bladder cancer: IMvigor211 study did not meet its primary endpoint of overall survival compared to chemotherapy
The phase III IMvigor211 study, that evaluated Atezolizumab ( Tecentriq ) in people with locally advanced or metastatic urothelial cancer ( mUC ) whose disease progressed during or after treatment with a Platinum-based chemotherapy ( previously treated ), did not meet its primary endpoint of overall survival ( OS ) compared to chemotherapy.
The safety profile observed in IMvigor211 was consistent with what has been previously observed for Atezolizumab.
The results observed in people treated with Atezolizumab in IMvigor211 were generally consistent with those observed in a similar group of people in the phase II IMvigor210 study.
The IMvigor211 data will be further examined in an effort to better understand these results, including the initial observation that the chemotherapy arm results were better than study design assumptions.
Atezolizumab is a monoclonal antibody designed to bind with a protein called PD-L1. It is designed to bind to PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Atezolizumab may enable the activation of T cells. Atezolizumab may also affect normal cells.
Tecentriq was granted accelerated approval by the U.S. Food and Drug Administration ( FDA ) based on tumour response rate and duration of response in IMvigor210 for the treatment of people with locally advanced or mUC who have disease progression during or following Platinum-based chemotherapy, or whose disease has worsened within 12 months of receiving Platinum-based chemotherapy before surgery ( neoadjuvant ) or after surgery ( adjuvant ).
IMvigor211 was a randomised pivotal study designed to support full approval globally and to serve as the confirmatory study to convert the accelerated approval to full approval in the US.
The FDA recently granted accelerated approval to Tecentriq as an initial treatment for people with locally advanced or mUC who are not eligible for Cisplatin chemotherapy.
A phase III pivotal study, IMvigor130 is currently ongoing in this population.
IMvigor211 is the first randomised phase III study of Atezolizumab compared to chemotherapy in people with advanced bladder cancer who were previously treated with a Platinum-based chemotherapy.
The study evaluated the efficacy and safety of Atezolizumab compared to chemotherapy ( Vinflunine, Paclitaxel or Docetaxel ) administered every three weeks in 931 people with previously-treated mUC who progressed during or following a Platinum-based regimen.
Eligible patients had an Eastern Cooperative Oncology Group ( ECOG ) performance status of 0-1, an evaluable tumor sample for centralised PD-L1 testing and had received at least one prior therapeutic regimens for mUC or who had developed mUC within 12 months of receiving Platinum-based chemotherapy before surgery ( neoadjuvant ) or after surgery ( adjuvant ).
The primary efficacy endpoint was overall survival and key secondary endpoints include objective response rate, progression-free survival, duration of response and safety.
The primary efficacy endpoint, overall survival, was to be tested in a successive fashion in study populations defined by PD-L1 expression.
The first population tested was people with the highest levels of PD-L1 expression ( IC2/3 ), followed by those with any level of PD-L1 expression ( IC1/2/3 ), and followed by the overall study population ( Intention-To-Treat; ITT ).
Statistical significance needed to be achieved in the IC2/3 population in order to evaluate the IC1/2/3 population for statistical significance, and similarly achieved in the IC1/2/3 population in order to evaluate the overall study population for statistical significance.
Metastatic urothelial cancer is associated with a poor prognosis and limited treatment options. Until Tecentriq’s approval in the US in May 2016 there had been no major advances for more than 30 years.
Urothelial cancer is the ninth most common cancer worldwide, with 430,000 new cases diagnosed in 2012, and it results in approximately 145,000 deaths globally each year. Men are three times more likely to suffer from urothelial cancer, compared with women, and the disease is three times more common in developed countries than in less developed countries. ( Xagena )
Source: Roche, 2017