Status:
Open
Clinicaltrials.gov identifier:
Sponsor:
Merck Sharpe and Dohme
Enrollment:
1010
Study Design:
This was a global, randomized open label phase 3 trial comparing pembrolizumab alone or combined with platinum-based chemotherapy versus chemotherapy as first line treatment for patients with locally advanced or metastatic UC. Patients were randomized 1:1:1 to pembrolizumab and chemotherapy (n=351) or pembrolizumab alone (n= 307) or chemotherapy alone (n=352).
Rationale:
The current standard for first line treatment in advanced UC is cisplatin-based chemotherapy. Pembrolizumab is recommended for patients as second line therapy or as first line therapy in patients that are PDL-1 positive and ineligible for platinum. Avelumab is recommended as maintenance treatment for patients who do not progress on first line chemotherapy.
Endpoints:
There were dual primary endpoints, progression free survival (PFS) per RECIST by blinded independent review and overall survival (OS).
Comments:
The results of this trial were unexpected as pembrolizumab is approved for metastatic disease as well as BCG unresponsive non-muscle invasive bladder cancer. The results seem to close the door for combination chemotherapy and immunotherapy in the front-line setting. In a somewhat similar study with atezolizumab, the combination led to improvement in PFS, but OS has yet to be reported.
Results:
The combination of immunotherapy and chemotherapy did not reach statistical significance for PFS or OS in patients with untreated locally advanced or metastatic UC.
