Immune blockade treatment promising for advanced bladder cancer

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The antibody MPDL3280A, which blocks the protein PD-L1, resulted in tumor shrinkage in 52% of patients with advanced bladder cancer. PD-L1 is thought to help cancer cells evade immune detection.

This represents a breakthrough in developing a new therapy for advanced bladder cancer, which has had no major treatment advances in the past 30 years. The study, conducted by scientists from Queen Mary University of London, was published in Nature (2014; doi:10.1038/nature13904).

In a phase one, multicenter international clinical trial, 68 patients with advanced bladder cancer (who had failed all other standard treatments such as chemotherapy) received MPDL3280A, a cancer immunotherapy medicine being developed by Roche. In addition, patients were all tested for the protein PD-L1 and around 30 were identified as having tumors positive for PD-L1.

After 6 weeks of treatment, 43% of PD-L1-positive patients found their tumor had shrunk. This rose to 52% after 12 weeks of follow up. In two of these patients (7%) radiological imaging found no evidence of the cancer at all following the treatment. Among PD-L1 negative patients, 11% responded positively to treatment too.

Patients who had a positive response to treatment found the benefits were prolonged, and safety results were also encouraging, with fatigue and loss of appetite most commonly reported as side effects.

The early results of this trial are so promising that the MPDL3280A antibody drug has been given breakthrough therapy designation status by the US FDA.

"This study is a hugely exciting step forward in the search for alternative advanced bladder cancer treatment,” said Tom Powles, MD, lead author and consultant medical oncologist, Barts Cancer Institute, Queen Mary University of London. “For decades chemotherapy has been the only option, with a poor outcome and many patients too ill to cope with it. Not only has this investigational drug had a striking response rate, we can target this therapy for patients by screening specific protein PD-L1.

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