Posted: December 12, 2014

The treatment of metastatic bladder cancer has stalled out.  After initial optimism with the use of MVAC in the 1980’s and the addition of Gemcitabine and Docetaxel more recently where up to 50% of patients showed some evidence of benefit, barriers to success remain — chiefly the toxicity of the regimen, especially in older patients, and the rapid emergence of drug resistance.  A new class of monoclonal antibodies with activity against the PD-1 protein and PD-L1 receptors have helped unmask the immunogenicity of cancer cells and make them susceptible to attack by the body’s immune system.  One of these proteins is MPDL3280A a monoclonal antibody that has shown activity against melanoma.  This protein doesn’t even have a generic name yet it is so new.  Now investigators have taken this molecule and used it to treat patients with metastatic urothelial cancer – chiefly bladder cancer and have found stunning results in an admittedly small group of patients.   Up to half of all the cancer patients with the PD-1 protein on their tumor infiltrating lymphocytes benefited from this treatment.  The responses were rapid and durable, and toxicity was much less than that seen with conventional chemotherapy.  The report appeared in Nature ; Dr. Stark can provide the complete reference, although it is quite technical and a difficult read.  He comments, “We have been waiting for a new approach to bladder cancer for a long time.  Conventional chemo has hit the efficacy wall and adding more cytotoxic drugs hasn’t seemed fruitful for a long time.  This approach, helpful in melanoma, has now been extended to urothelial cancer.  This entire field is brand new in the treatment of this difficult family of diseases and offers much promise.”

Update 2020: in the six years since this posting was first created, not much has happened.  Authorities still recommend cis-platin based chemotherapy as first-line treatment.  Pembrolizumab, the most popular anti PD-1 treatment is reserved for platinum-intolerant or platinum-failed patients.  Although the overall response rate for Pembro was only 29% in a recent trial, many responses were durable and median duration of response had not been reached at the time the paper was published.   Dr. Stark weighs in: “The urologic community has always been slow to adopt new treatments.  At the time preop chemo was known to be better than surgery alone, urologists were not getting it for their patients.  This is no exception.  If a more robust, less heavily pre-treated class of patients were treated, I suspect Pembro would be shown to be far superior.  Chemo for bladder cancer hasn’t changed in 30 years.  It’s time to move on.”