FDA Approves Atezolizumab for Treatment of Urothelial Carcinoma

FDA also approved the PD-L1 diagnostic assay to detect PD-L1 protein expression levels on patients’ tumour-infiltrating immune cells

On 18 May, 2016 the US Food and Drug Administration (FDA) approved atezolizumab (Tecentriq) to treat the urothelial carcinoma. This is the first product in its class (PD-1/PD-L1 inhibitors) approved to treat bladder cancer. The FDA also approved the PD-L1 diagnostic assay to detect PD-L1 protein expression levels on patients’ tumour-infiltrating immune cells and help physicians determine which patients may benefit most from treatment with atezolizumab.

Atezolizumab targets the PD-1/PD-L1 pathway. By blocking these interactions, it may help the body’s immune system fight cancer cells. It is the first FDA-approved PD-L1 inhibitor and the latest in the broader class of PD-1/PD-L1 targeted biologics approved by the FDA in the last two years.

Atezolizmab is approved for the treatment of patients with locally advanced or metastatic urothelial carcinoma whose disease has worsened during or following platinum-containing chemotherapy, or within 12 months of receiving platinum-containing chemotherapy, either before (neoadjuvant) or after (adjuvant) surgical treatment.

The safety and efficacy of atezolizumab were studied in a single-arm clinical trial involving 310 patients with locally advanced or metastatic urothelial carcinoma. This trial measured the objective response rate. The study also looked at the difference in effect based on “positive” versus “negative” expression of the PD-L1 protein on patients’ tumour-infiltrating immune cells.

In all patients, 14.8% of participants experienced at least a partial shrinkage of their tumours, an effect that lasted from more than 2.1 to more than 13.8 months at the time of the response analysis. In patients who were classified as “positive” for PD-L1 expression, 26% of participants experienced a tumour response compared to 9.5% of participants who were classified as “negative” for PD-L1 expression.

While patients who received atezolizumab experienced a tumour response across the study, the greater effect in those who were classified as “positive” for PD-L1 expression suggests that the level of PD-L1 expression in tumour-infiltrating immune cells may help identify patients who are more likely to respond to treatment with atezolizumab. Therefore, on 18 May 2016, the FDA also approved the Ventana PD-L1 (SP142) assay to detect PD-L1 protein expression levels on patients’ tumour-infiltrating immune cells and help physicians determine which patients may benefit most from treatment with atezolizumab.

The most common side effects of treatment with atezolizumab were fatigue, decreased appetite, nausea, urinary tract infection, pyrexia and constipation. Atezolizumab also has the potential to cause infection and immune-mediated side effects. These severe immune-mediated side effects involve healthy organs, including the lung, colon and endocrine system.

The FDA granted the atezolizumab application breakthrough therapy designation, priority review status and accelerated approval for this indication. These are distinct programmes intended to facilitate and expedite the development and review of certain new drugs in light of their potential to benefit patients with serious or life-threatening conditions.

Tecentriq is marketed by Genentech based in San Francisco, California. The Ventana PD-L1 (SP142) assay complementary diagnostic for Tecentriq is marketed by Ventana Medical Systems, based in Tucson, Arizona.