AUA 2018: Refining Immunotherapy Combinations and Sequencing in Bladder Cancer

San Francisco, CA ( Joaquim Bellmunt, MD presented his thoughts on how we are able to refine immunotherapy combinations in patients with advanced urothelial carcinoma of the bladder as part of the basic science lectures at the combined meeting of the Society of Urologic Oncology (SUO) and Society for Basic Urologic Research (SBUR) at the American Urological Association’s 2018 meeting in San Francisco, CA. 

He began by discussing the evolution of systemic therapy for urothelial carcinoma was somewhat stagnant over the last decade, however, in the last 2 years, we now have multiple newly-approved treatment agents.  He noted that immunotherapy is an exciting and well-tolerated agent in the treatment of urothelial carcinoma, however, only 15-20% of patients derive significant benefit from this treatment. Bellmunt believes that there are multiple questions that need to be clarified for immunotherapy to be used its maximal potential.  Sequential versus combination therapy immunotherapy is an area that needs to be studied in depth. 

He noted that there are three main categories of possible synergistic combinations of immune checkpoint inhibitors and other therapeutic agents.  The first of these is combination immune checkpoint inhibitors. There are ongoing trials that will help us to determine if combination immunotherapy or immunochemotherapy are superior to immune checkpoint inhibitor monotherapy.  These studies include KEYNOTE-361, ImVigor 130, DANUBE, and CheckMate 901.  These studies will also help to answer questions regarding the role of sequential therapy versus combination therapy. 

The second category of therapeutic agents that could potentially be combined with immunotherapy are targeted therapies, of which there are multiple metabolic pathways that could be exploited by agents such as arginase, epacadostat, adenosine, tryptophan.  All of these agents have been shown in some way to modulate the immune system and may be synergistic with immune checkpoint inhibitors. 

The third category of potential therapy to combine with immune checkpoint inhibitors include vaccine agents.  He believes that as we come into the personalized medicine era, this approach may be shown to be beneficial, however, these combination trials with vaccines are in their infancy. 

Bellmunt then focused on the fact that we are learning a great deal about how sequential therapy with immunotherapy followed by chemotherapy may improve responses to both agents. He believes that there may be a role to use immunotherapy to prime a patient’s tumor to receive eventual chemotherapy.  There are trials that are ongoing, however, there are no definitive results yet. 

He concludes that as we learn more about the genetic and molecular pathways that contribute to urothelial carcinoma from entities such as The Cancer Genome Atlas (TCGA), and as better biomarkers become available to predict response to treatment, we will improve on the ability to successfully treat patients with metastatic disease. 

Presented by: Joaquim Bellmunt, MD, Ph.D., Harvard Medical School

Written by: Brian Kadow, MD. Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Philadelphia PA at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA