Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial

Background: Few options exist for patients with locally advanced or metastatic urothelial carcinoma after progression with platinum-based chemotherapy. We aimed to assess the safety and efficacy of atezolizumab (anti-programmed death-ligand 1 [PD-L1]) versus chemotherapy in this patient population. Methods: We conducted this multicentre, open-label, phase 3 randomised controlled trial (IMvigor211) at 217 academic medical centres and community oncology practices mainly in Europe, North America, and the Asia-Pacific region. Patients (aged ≥18 years) with metastatic urothelial carcinoma who had progressed after platinum-based chemotherapy were randomly assigned (1:1), via an interactive voice and web response system with a permuted block design (block size of four), to receive atezolizumab 1200 mg or chemotherapy (physician's choice: vinflunine 320 mg/m2, paclitaxel 175 mg/m2, or 75 mg/m2 docetaxel) intravenously every 3 weeks. Randomisation was stratified by PD-L1 expression (expression on <1% [IC0] or 1% to <5% [IC1] of tumour-infiltrating immune cells vs ≥5% of tumour-infiltrating immune cells [IC2/3]), chemotherapy type (vinflunine vs taxanes), liver metastases (yes vs no), and number of prognostic factors (none vs one, two, or three). Patients and investigators were aware of group allocation. Patients, investigators, and the sponsor were masked to PD-L1 expression status. The primary endpoint of overall survival was tested hierarchically in prespecified populations: IC2/3, followed by IC1/2/3, followed by the intention-to-treat population. This study, which is ongoing but not recruiting participants, is registered with ClinicalTrials.gov, number NCT02302807. Findings: Between Jan 13, 2015, and Feb 15, 2016, we randomly assigned 931 patients from 198 sites to receive atezolizumab (n=467) or chemotherapy (n=464). In the IC2/3 population (n=234), overall survival did not differ significantly between patients in the atezolizumab group and those in t