Pembrolizumab alone or combined with chemotherapy versus chemotherapy alone as first line therapy for advanced urothelial carcinoma (UC): Keynote 361

Merck Sharpe and Dohme
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).
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.
There were dual primary endpoints, progression free survival (PFS) per RECIST by blinded independent review and overall survival (OS).
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.
The combination of immunotherapy and chemotherapy did not reach statistical significance for PFS or OS in patients with untreated locally advanced or metastatic UC.