Immunotherapy In Bladder Cancer
For many years chemotherapy was the only treatment for bladder cancer and notoriously was not very effective and is very toxic. The treatment for bladder cancer has evolved with five new immunotherapy drugs FDA approved between 2016 and 2017.
The new drugs are all PDL1 inhibitors atezolizumab, avelumab, durvalumab, nivolumab, pembrolizumab. These drugs have been approved in the metastatic setting after the patient has progressed on a platinum treatment.
Two check point inhibitors are approved in the first line for patients who are cisplatin ineligible patients with poor renal function or patients with poor performance status. In such setting, atezolizumab and pembrolizumab can be given first line.
Atezolizumab given in first line setting as single agent had a response rate of 23% complete response 9% with a median survival of 16 months. In general the drug was well tolerated.
Pembrolizumab had a response rate of 29% with a complete response of 7% and more than 2/3 of the responses were durable.
Scans should be repeated every three months after starting therapy to avoid pseudo progression.
All the PDL1 inhibitors have similar immune related side effects. Endocrine hypothyroidism, hyperthyroidism, adrenal insufficiency, hypophysitis pulmonary pneumonitis, interstitial lung disease, GI hepatitis, Nervous System neuropathy, uveitis, Cardiac myocarditis, colitis, GI perforation, Renal nephritis, and skin dermatitis.
In general, the incidence of side effects is in the grade 1 or 2 level of toxicity which resolves by steroid administration.
Rarely toxicity has been grade 4 requiring discontinuation of the drug.
Current research is combining check point inhibitors with chemotherapy for improved results. Recent data shows that in the first line metastatic setting chemotherapy showed higher response rates after immunotherapy. Phase III studies are in progress.