EAU 2017: State-of-the-art Lecture: How will Immunotherapy Change the Treatment Paradigm?

London, England (UroToday.com) Dr. Robert Jones from Glasgow presented the role of immunotherapy in the current treatment paradigm of bladder urothelial carcinoma. At present, there are two anti-PD-1 inhibitors (pembrolizumab, nivolumab), three anti-PD-L1 inhibitors (atezolizumab, avelumab, durvalumab) and two CTLA-4 inhibitors (tremelimumab, ipilimumab) under evaluation. Only nivolumab and atezolizumab have received FDA approval, in the second line setting. Pembrolizumab should be approved in the second line shortly, given the recent head-to-head comparison of pembrolizumab to chemotherapy showing improved overall survival (OS) (HR 0.73, 95%CI 0.59-0.91). As Dr. Jones notes, “immune checkpoint inhibitors set a clear new standard of care and the role, if any, of second line chemo is unclear.” In the first line, data presented at ESMO 2016 from a phase Ia study looking at atezolizumab showed an objective response rate of 27% with a median duration of response of 22 months and 40% of responders having ongoing responses at the time of data cutoff. At this time, there are three first line phase III clinical trials for patients with metastatic urothelial carcinoma, all with three arms in each study (generally, arm 1: immune checkpoint inhibitor, arm 2: immune checkpoint inhibitor in combination with chemotherapy, arm 3: chemotherapy). We eagerly await these results.

The current paradigm for metastatic urothelial carcinoma is that the disease is a universally fatal condition and the aim of treatment is palliation. Many patients are currently unsuitable for or choose not to receive chemotherapy. Immunotherapy has given us the optimism to suggest that maybe metastatic urothelial carcinoma doesn’t have to be a universally fatal disease. As Dr. Jones mentions, long-term follow-up of clinical trials is essential, considering that median follow-up for the pembrolizumab vs chemotherapy trial was only 14 months. The BISCAY trial, a phase Ib, biomarker-directed study of patients with metastatic bladder cancer may even allow precision medicine in this typically dismal setting.

Dr. Jones concluded this thought provoking session by noting that immunotherapy is here to stay as second line treatment and we urgently need to understand patient selection in the first line setting. Ultimately, we need careful research to “harness the power of all available therapy to improve cure rates in muscle-invasive bladder cancer.”

Speaker(s): Robert Jones, University of Glasgow, Glasgow, UK

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto - Twitter: @zklaassen_md at the #EAU17 - March 24-28, 2017- London, England