Roche has announced that a phase 3 study of atezolizumab (Tecentriq) in patients with locally advanced or metastatic urothelial cancer (mUC) did not meet its primary endpoint of improved overall survival compared with chemotherapy.
Atezolizumab is a monoclonal antibody designed to bind with programmed death ligand 1 (PD-L1) proteins expressed on tumor cells and on tumor-infiltrating immune cells, thereby blocking their interactions with both programmed death 1 (PD-1) and B7.1 receptors. By inhibiting PD-L1, atezolizumab may enable the activation of T cells. Atezolizumab may also affect normal cells.
The IMvigor211 trial was the first randomized late-stage study of atezolizumab compared with chemotherapy in patients with advanced bladder cancer who were previously treated with platinum-based chemotherapy. The study evaluated the efficacy and safety of atezolizumab compared with that of chemotherapy (vinflunine, paclitaxel, or docetaxel) administered every three weeks in 931 patients with mUC who had progressed during or after a platinum-based regimen.
According to a Reuters report, the study’s disappointing results have raised questions about whether regulators should scale back their approval of atezolizumab. Last May, Roche won fast-track approval in the United States for the medication against bladder cancer, but full approval hinged on the results of further trials.
Reuters quoted a market analyst as saying: “This puts the existing U.S. bladder cancer approval in serious doubt, and will also, of course, raise market concerns about Tecentriq’s efficacy in other cancer types.”
The drug, also approved for lung cancer, is a pillar of Roche’s cancer-drug strategy, according to Reuters, and is seen by its scientists as a backbone for multiple combinations with other drugs to fight various forms of the disease. The company has more than 30 trials ongoing with atezolizumab.
The failure of atezolizumab is the latest instance where cancer immunotherapies have not lived up to their promise of revolutionizing treatment, Reuters points out. Last year, nivolumab (Opdivo, Bristol Myers-Squibb), an antibody that blocks PD-1 receptors, failed to perform better than older chemotherapies.