Anti-PD-L1 Therapy in Muscle-Invasive Bladder Cancer

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Numerous checkpoint blockade inhibitors are being tested in bladder cancer, with the current front-runner being atezolizumab (formally MPDL3280A), a PD-L1 inhibitor that has shown activity in muscle-invasive bladder cancer, says Dean F. Bajorin, MD. Atezolizumab was explored in 68 patients with metastatic urothelial bladder cancer who received prior chemotherapy in a phase I trial. The objective response rate with atezolizumab was 43% in patients with PD-L1-positive disease.

The agent is relatively well tolerated, without major toxicities, adds Bajorin. Fatigue, decreased appetite, and nausea were the most common adverse events. Based on these data, atezolizumab received a breakthrough therapy designation from the FDA in June 2014.

The current findings that correlate biomarkers with disease response are not based on real-time assays, cautions Evan Y. Yu, MD. Many of the tissue samples originated from transurethral resections from cystectomies that were performed months or years earlier. Tumors may evolve over time and PD-L1 expression patterns may change as well, Yu adds, particularly when exposed to factors such as smoking, bacillus Calmette-Guerin (BCG), and prior chemotherapy.

Based on some of these studies, the benefits from therapy are being redefined, comments Bajorin—while most studies currently examine the extent of tumor shrinkage, benefit may lie not simply in disease reduction but also in lack of disease progression, as well as the ability to tolerate treatment, which is an important consideration for patients.