A Study of Pembrolizumab (MK-3475) Versus Paclitaxel, Docetaxel, or Vinflunine for Participants With Advanced Urothelial Cancer (MK-3475-045/KEYNOTE-045)

Study Design: 
This is a Phase III, randomized clinical trial comparing pembrolizumab for up to 2 years to chemotherapy in terms of OS and PFS. The chemotherapy regimen consists of either paclitaxel, docetaxel, or vinflunine and in a recent amendment, patients are able to crossover to receive pembrolizumab if they experience disease progression with chemotherapy. Eligibility is limited to patients with histologically confirmed UC with measurable disease after previous platinum therapy.
Until recently, there were limited options for patients with locally advanced/unresectable urothelial cancer (UC) that has recurred or progressed after combination platinum-based chemotherapy. Given the activity of PD-1/PD-L1 inhibitors in the metastatic setting, this randomized trial aims to compare the impact of pembrolizumab on overall survival (OS) and progression-free survival (PFS) compared to chemotherapy (investigator’s choice of paclitaxel, docetaxel, or vinflunine). Previous Phase III results demonstrated longer OS in the pembrolizumab group and the updated results were presented at ESMO.
Additional follow-up confirms superior OS of pembrolizumab immunotherapy over chemotherapy as second-line treatment after cisplatin based combination chemotherapy.
With median follow-up of 22.5 months for both treatment arms, median OS was significantly longer in the pembrolizumab arm in all patients (10.3 vs. 7.4 months; HR 0.70, p = 0.0003) which was an improvement over the earlier analysis with HR of 0.73. In patients with PD-L1 combined positive score (CPS; % of PD-L1 expressing tumor and inflammatory cells) 10%, median OS was also improved with pembrolizumab vs. chemotherapy (8.0 vs. 5.2 months; HR 0.58, p=0.003). The overall response rate was greater with pembrolizumab (21.1% vs. 11.0%) and treatment-related AEs of any grade were fewer (62.0% vs. 90.6%). However, PFS was not statistically different between the groups.