This is an evolving field. While the thought had been all the drugs were likely equivalent in efficacy (with no head to head trials) this has changed in the past week. Roche had a press release in which they announced the Phase III IMvigor211 study that evaluated atezolizumab in people with locally advanced or metastatic urothelial cancer (mUC) whose disease progressed during or after treatment with a platinum-based chemotherapy (previously treated) did not meet its primary endpoint of overall survival (OS) compared to chemotherapy. At the same time, pembrolizumab has just been granted approval in the second line as well as an accelerated approval in the cisplatin ineligible patients. Given the survival benefit vs chemotherapy of 3 months (Belmunt et al, N Engl J Med 2017; 376:1015-1026) that was not seen with atezolizumab, Pembrolizumab will be my preferred immunotherapy going forward pending additional data given its superior OS compared to chemotherapy and its q3week dosing schedule (compared to q2week dosing schedule for the other 3 drugs).

The therapeutic landscape for metastatic and locally-advanced urothelial cancers of the bladder and urinary tract has undergone significant paradigm change in the last few years with the introduction of anti-PD1/PDL1 immune checkpoint inhibitors. To date, five agents are approved by FDA, including anti-PD1 agents nivolumab and pembrolizumab, and anti-PDL1 agents atezolizumab, durvalumab and avelumab in the platinum-refractory setting. Atezolizumab and pembrolizumab have also received FDA approval for cisplatin-ineligible patients with advanced urothelial cancers. There are no trials comparing these agents to one another and there is unlikely to be one in the near future. While cross-trial comparison is generally discouraged, a quick survey across all relevant studies showed comparable response and toxicity rates. In our cohort, anti-PD1 versus anti-PDL1 agent was not a significant predictor of response in univariate analysis nor did the choice of agents confer any statistical interactions with DDR status. In clinical practice, pembrolizumab has the most robust clinical evidence in the platinum-refractory setting, as supported by the phase III KEYNOTE-045 which demonstrated survival advantage against investigators’ choice of cytotoxic chemotherapy. (Bellmunt et al NEJM 2017) At the time of writing, there are no biomarkers or selection criteria to select one agent over another, or immune checkpoint inhibitors over carboplatin-based chemotherapy in the first-line cisplatin naive, apart from availability, access to drug and treatment schedule.