SUO 2017: Bladder Cancer: Currently Approved Immunotherapy

Washington, DC ( Dr. Pilmack gave an interesting talk on current approved immunotherapy for bladder cancer. Prior to 2016, no immunotherapy was available for bladder cancer patients in any setting. However, nowadays, there are immunotherapy drugs which are FDA approved and available in the setting of 1st line and 2nd line metastatic patients. Currently Pembrolizumab is FDA approved for post platinum therapy, and other treatments will be approved in the near future as well, including Atezolizumb, Nivolumab, Durvalmab and Avelumab.

Keynote-43 was the study that resulted in the approval of Pembrolizumab, randomizing urothelial carcinoma patients after 1-2 lines of platinum based chemotherapy, to either Pembrolizumab or additional chemotherapy. This study demonstrated an objective response rate (ORR) for all patients in the study of 21.1% and a 20.3% ORR specifically for patients who were PD-L1 positive. The study also showed a significant advantage for Pembrolizumab in progression free survival (PFS) and overall survival (OS). The overall safety profile of the drug was significantly better than chemotherapy, making it even more attractive in this setting. This resulted in an improved quality of life, shown by Keynote-45 as well.

IMvigor 211 was another study randomizing patients with progression during or following platinum based chemotherapy, to either Atezolizumab or additional chemotherapy. This showed a non-statistically significant advantage for Atezolizumab in the PD-L1 positive population, but a significant advantage in the intention to treat (ITT) population.

There were also phase 2 studies performed in patients post platinum based chemotherapy, analyzing Durvalumab, Nivolumab, and Avelumab. These studies all resulted in accelerated FDA approval of these drugs. All of these drugs currently provide an overall response rate of between 13-21.1% in post platinum based chemotherapy patients, with a clear advantage in 12 month overall survival. Furthermore, the safety profile of these drugs is very appealing, with grade 3-5 treatment related adverse effects of between 6.8-21%.

There are also trials assessing the role of first line PD1 pathway inhibition in cisplatin ineligible patients. Atezolizumab was tested in this setting, demonstrating a complete response (CR) rate of 9% and ORR of 23%. Pembrolizumab was also assessed in this setting showing an ORR of 24% and CR of 5%.

Dr. Pilmack concluded her great presentation by stating that there are also some data showing the response rate can persist after treatment discontinuation, but this is still not clearly known. Other questions that need to be answered include whether there are biomarkers which are better than PDL1 IHC, and which subset of patients responds best to PDL1 inhibition.

Presented by: Elizabeth R. Plimack, MD, Fox Chase cancer center, USA

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, @GoldbergHanan, at the 18th Annual Meeting of the Society of Urologic Oncology, November 29-December 1, 2017 – Washington, DC