BACKGROUND: Platinum-based chemotherapy is standard-of-care first-line treatment 
for advanced urothelial carcinoma. However, progression-free survival and 
overall survival are limited by chemotherapy resistance.
METHODS: In a phase 3 trial, we randomly assigned patients with unresectable 
locally advanced or metastatic urothelial cancer who did not have disease 
progression with first-line chemotherapy (four to six cycles of gemcitabine plus 
cisplatin or carboplatin) to receive best supportive care with or without 
maintenance avelumab. The primary end point was overall survival, assessed among 
all patients who underwent randomization (overall population) and among those 
with tumors positive for programmed cell death ligand 1 (PD-L1). Secondary end 
points included progression-free survival and safety.
RESULTS: Among all 700 patients who underwent randomization, the addition of 
maintenance avelumab to best supportive care significantly prolonged overall 
survival as compared with best supportive care alone (control). Overall survival 
at 1 year was 71.3% in the avelumab group and 58.4% in the control group (median 
overall survival, 21.4 months vs. 14.3 months; hazard ratio for death, 0.69; 95% 
confidence interval [CI], 0.56 to 0.86; P = 0.001). Avelumab also significantly 
prolonged overall survival in the PD-L1-positive population; overall survival at 
1 year was 79.1% in the avelumab group and 60.4% in the control group (hazard 
ratio, 0.56; 95% CI, 0.40 to 0.79; P<0.001). The median progression-free 
survival was 3.7 months in the avelumab group and 2.0 months in the control 
group in the overall population (hazard ratio for disease progression or death, 
0.62; 95% CI, 0.52 to 0.75) and 5.7 months and 2.1 months, respectively, in the 
PD-L1-positive population (hazard ratio, 0.56; 95% CI, 0.43 to 0.73). The 
incidence of adverse events from any cause was 98.0% in the avelumab group and 
77.7% in the control group; the incidence of adverse events of grade 3 or higher 
was 47.4% and 25.2%, respectively.
CONCLUSIONS: Maintenance avelumab plus best supportive care significantly 
prolonged overall survival, as compared with best supportive care alone, among 
patients with urothelial cancer who had disease that had not progressed with 
first-line chemotherapy. (Funded by Pfizer and Merck [Darmstadt, Germany]; 
JAVELIN Bladder 100 ClinicalTrials.gov number, NCT02603432.).