Important caveats of KEYNOTE-045: relevance of these findings in the current and future therapeutic paradigm

Urothelial carcinoma of bladder is the fourth most common cancer in men in United States and ninth most common cancer worldwide (1). It is estimated that in 2018, there will be 81,190 new cases and 17,240 deaths due to bladder cancer in United States (US) (2). Although most patients (70%) have non-muscle invasive bladder cancer (NMIBC) (T0–T1), 30–40% have muscle invasive bladder cancer (MIBC) (T2–T4a) and around 5% have metastatic urothelial carcinoma (MUC) at presentation (3). MUC has a high mortality rate with therapeutic options for those with advanced disease being up until recently limited. The standard platinum-based chemotherapy has for the most part remained the first line option for patients exhibiting this unfortunate diagnosis but, if and once platinum-based regimen fail, there is no largely accepted consensus about which treatment should be offered next. Vinflunine was approved as a treatment option for post-platinum recurrent disease in Europe (4,5). However, in US, patients were receiving single-agent chemotherapy regimens (e.g., taxanes) with response rates of around 10% and median survival of 6 to 8 months (6,7)