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EAU 2017 | Overview of urothelial carcinoma treatment landscape – the promise of immunotherapy

Joaquim Bellmunt, MD, PhD, from the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, discusses recent advances in treating genitourinary malignancies at the European Association of Urology conference 2017 in London, UK. Focusing on immune-oncological agents in bladder cancer, the first-line treatment in patients with metastatic disease is platinum-based chemotherapy, with second-line therapy until recently also being chemotherapy-based, with only vinflunine approved in Europe. In the US, additional second-line agents were used, such as paclitaxel and docetaxel, however limited benefit was seen for patients with these. Recent advances in immune-oncological agents mean that this is now an option for bladder cancer treatment, with high efficacy seen. As many as 5 immuno-oncological compounds are currently being investigated for bladder cancer. Initially trials were carried out in patients failing first- and second-line therapy, and the PD-1 inhibitor nivolumab is now approved in the US for bladder cancer, as well as the PD-L1 inhibitor atezolizumab. Results from nivolumab show that around 25% of patients benefit from this treatment, and these patients have a prolonged response, in contrast to chemotherapy where responses are seen but these are limited and not durable. While the median duration of response to chemotherapy is around 3 – 4 months, immunotherapy responses are persisting for longer. Dr Bellmunt suggests that immunotherapy establishes a permanent immune response which prevents the tumor from recurring. The Phase III KEYNOTE-045 trial (NCT02256436) directly compared standard of care chemotherapy and pembrolizumab immunotherapy as second-line therapy in 545 advanced urothelial carcinoma patients failing platinum-based chemotherapy. A significant improvement was seen in response rate (RR), with indications that the median duration of response will also be longer in immunotherapy-treated patients. In addition, immunotherapy showed a better toxicity profile and superior health-related quality of life. He concludes that immunotherapy will in future be the standard of care for second-line treatment of advance urothelial carcinoma, although he points out that these results need to be built upon in additional trials, as well as testing combination approaches.