Bladder cancer is a common cancer, and about 10% of patients are diagnosed at an advanced stage (which means the cancer has spread to other parts of the body). This makes treatment very difficult, and chemotherapy is the only option. Patients have an average survival time of 12-18 months after diagnosis, and the toxicity of chemotherapy and limited survival benefit cause many to abandon treatment. Scientists at Queen Mary, University of London, have made a major breakthrough by developing a new treatment for advanced bladder cancer, knowing that there have been no major advances in bladder cancer treatment in the last 30 years. They detected MPDL3280A, an antibody that blocks the PD-L1 protein, which is known to help cancer cells evade immune detection and grow vigorously in the body. The study has been published in the journal Nature. In a phase I clinical trial, 68 patients with advanced bladder cancer (who were not treated with all other standard treatments such as chemotherapy) received MPDL3280A. These patients were tested for PD-L1 protein, and approximately 30% were determined to have PD-L1-positive tumors. After only 6 weeks of treatment, 43% of the PD-L1-positive patients found their tumors to be shrinking. This percentage rose to 52% after 12 weeks of follow-up. In two of these patients (7%), post-treatment radiography did not reveal any signs of cancer. Of the PD-L1-negative patients, 11% also showed a response to treatment. The study also found that the effects of this treatment were long-term; the safety profile was also encouraging, with side effects including only the most common symptoms of fatigue and loss of appetite. Dr. Tom Powles, lead author of the paper and consultant medical oncologist at the Barts Cancer Institute, Queen Mary, University of London, said, “This study is a very exciting step toward finding an effective alternative treatment for advanced bladder cancer. For decades, chemotherapy was the only option, its clinical outcomes were poor, and many patients were too sick to tolerate it. This new therapy not only has a remarkable response rate, but it also improves that response rate by screening patients for the specific target protein PD-L1.” The results of this trial are so promising that the MPDL3280A antibody drug has received breakthrough therapy designation from the FDA. Several studies are further testing the drug in Europe and other parts of the world. Recently Roche Pharmaceuticals (Roche) announced the success of its Phase II clinical study of atezolizumab (MPDL3280A), a PD-L1 antibody, for the treatment of bladder cancer. The results of the study showed that atezolizumab resulted in a reduction in tumor size in a specific range of bladder cancer patients. Such results helped the FDA to expedite approval of this breakthrough therapy. For Roche, the success of the Phase II trial was based on the study’s second cohort of patients with locally advanced bladder cancer or uroepithelial carcinoma of the bladder, some of whom continued to have disease that worsened during chemotherapy. The primary objective of the trial was to validate the overall response rate to atezolizumab, with secondary objectives including duration of response, overall survival, progression-free survival, and safety. Roche also said that the higher the expression of PD-L1, the more dramatic the response to the drug, which could allow the drug to have a more pronounced and rapid effect in driving the immune system to fight cancer cells. PD-1 and PD-L1 immunotherapy is a new and highly anticipated anti-cancer immunotherapy designed to use the body’s own immune system to fight cancer by blocking the PD-1 or PD-L1 signaling pathway causing cancer cell death, which has the potential to treat many types of tumors and is expected to substantially improve overall patient survival.