Overview of urothelial carcinoma treatment landscape – the promise of immunotherapy

Joaquim Bellmunt, MD, PhD, from the Dana-Farber Cancer Institute, 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.

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