Up-regulation of the programmed death ligand 1 (PD-L1) in patients with haematological malignancies and solid tumours increases the propensity for cancer cells to evade immune surveillance. Atezolizumab (Tecentriq™), a monoclonal antibody designed to inhibit PD-L1, enables T-cell activation, restoring their ability effectively detect and destroy tumour cells.

While atezolizumab is not currently authorised for use in Europe; in May 2016, the US Food and Drug Administration (FDA) approved atezolizumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma (MUC) whose disease progressed during or following platinum-based chemotherapy. FDA approval was based on results reported in cohort 2 of the phase II trial IMvigor 210. In cohort 2, 310 patients who failed platinum-based chemotherapy were stratified by PD-L1 expression, defined as the percentage of PD-L1 positive tumour-infiltrating immune cells (ICs): IC0 (<1%), IC1 (≥1% but ≤5%), IC2/3 (≥5%). The primary endpoint was confirmed objective response rate (ORR) as assessed by independent review; secondary endpoints included duration of response (DOR), progression free survival (PFS), overall survival (OS), and safety.

Compared to a historical ORR of 10%, treatment with atezolizumab significantly improved ORR in each pre-specified IC group (IC2/3: 27% [95% CI 19–37], p<0.0001; IC1/2/3: 18% [95% CI 13–24], p = 0.0004; all patients: 15% [95% CI 11–20], p = 0.0058). At a median follow-up of 12 months, the median DOR was not yet reached; continued responses were reported in 38 (84%) of 45 responders. The median PFS was 2.1 months and similar across the IC groups. Fatigue, the most common adverse event, was observed in 50 patients (16%); and was severe (grade 3–4) in 5 (2%) patients. Fifteen (5%) of patients experienced severe immune-mediated adverse events involving pneumonitis, abnormal liver function tests, rash and dyspnea.

Although it is the first PD-L1 inhibitor to receive approval based on the tumour response rate and durability reported in cohort 2 of the phase II trial IMvigor 210, patients were not followed long enough to adequately determine the median DOR, whether atezolizumab reduces mortality or prolongs survival for some or all responders, how treatment may affect disease progression or recurrence, or to identify all potential adverse events. Further studies are needed to examine patient reported outcomes (PROMs), patient reported experiences (PREMs), and quality of life measures to determine whether atezolizumab provides adequate clinical benefit in terms of improving the symptoms and severity of locally advanced and MUC.