Metastatic Bladder Cancer New Systemic Treatments
Bladder cancer is more common in elderly patients. First line treatment for bladder cancer is Cisplatin containing chemotherapy regimens. Often times elderly patients are Cisplatin ineligible because of renal impairment or poor performance status. Chemotherapy regimens (GemCis, MVAC) for bladder cancer have notoriously had fairly poor response rates and fairly high rates of toxicity.
A new class of drugs called checkpoint inhibitors have been effective in a number of solid tumors including bladder cancer. Checkpoint inhibitors block normal proteins on cancer cells, or the proteins on the
T-cells that respond to them, promoting cell death (PD1 or PD-L1 inhibitors).
Pembrolizumab is a checkpoint inhibitor that is FDA approved for metastatic bladder cancer. Pembrolizumab showed a 20% response rate as single agent and an improvement in overall survival compared to standard chemotherapy. Pembrolizumab compared to chemotherapy had a better safety profile with the most common side effects being fatigue, diarrhea, rash, poor appetite, and musculoskeletal pain.
When pembrolizumab was given in combination with epacadostat the response rate increased to 57% with 21% complete response rate. The most common side effects were fatigue and rash. Epacadostat is an agent that works on the immune microenvironment.
Another (PD-L1 inhibitor) checkpoint inhibitor FDA approved for front line treatment in Cisplatin eligible patients is atezolizumab with a response rate of 27%. It has a complete response rate of 10% and a two-year survival of 10%.
Two other checkpoint inhibitors FDA approved in May 2017 for urothelial carcinoma are avelumab and durvalumab.
Avelumab was approved second line after failure to respond to Cisplatin. The response rate was 13% with 5% complete response regardless of the PD-L1 expression.
The most common side effects were fatigue, infusion reaction, musculoskeletal pain, nausea, anorexia, and UTI.
Durvalumab was also FDA approved in Cisplatin failure metastatic urothelial carcinoma patients. The response rate in patients with high PD-L1 expression was 26% and 4% in patients with low PD-L1 expression the side effects were the same as avelumab.
Numerous other compounds are currently being investigated.