New Era of Bladder Cancer Treatments Has Begun

Andrea B. Apolo, MD

As part of Cancer Network’s coverage of the 2015 Genitourinary Cancers Symposium, today we are speaking with Andrea B. Apolo, MD, chief of the bladder cancer section in the genitourinary malignancy branch at the Center for Cancer Research at the National Cancer Institute. At this year’s meeting, Dr. Apolo presented an update on systemic therapies for urothelial tumors.

-Interviewed by Leah Lawrence 

Cancer Network: Dr. Apolo, thank you for speaking with us today.

Dr. Apolo: Thank you for having me.

Cancer Network: First, tell us, how common of a cancer is urothelial cancer?

Dr. Apolo: Urothelial carcinoma or bladder cancer is one of the most common malignancies in the United States. It is the sixth most common cancer in the United States. Last year, in 2014, there were over 74,000 new cases diagnosed and over 15,000 deaths that were attributed to bladder cancer.

Cancer Network: So tell us, is systemic chemotherapy the standard of care for these patients?

Dr. Apolo: Yes, systemic therapy is the standard of care for patients with metastatic urothelial carcinoma of the bladder, and cisplatin chemotherapy is the backbone of these therapies.

Cancer Network: Your presentation discussed what is new in systemic therapies for urothelial cancer. Can you briefly discuss what a few of these recent advances are?

Dr. Apolo: Sure, I focused my talk on two main areas of research in bladder cancer: (1) precision medicine and (2) immunotherapies.

In terms of precision medicine, I discussed ongoing efforts in translating patient-derived genomic profiles into precision therapy in clinical trials of urothelial cancer patients. I also discussed TCGA’s [The Cancer Genome Atlas] recent efforts published last year in a report of 131 muscle-invasive bladder cancer tumors and the most commonly mutated genes that were reported. Many of the genes have pathways that can potentially be targeted with therapeutic agents, such as PIK3CA, FGFR3, and TSC1. They actually reported in the TCGA report that 69% of the tumors harbor potentially therapeutic targets.

In terms of immunotherapy, we are currently in an immunotherapy revolution in oncology, and checkpoint inhibitors are leading the way. Urothelial carcinoma is one of a growing list of tumor types that respond to immune checkpoint inhibition. Two early-phase clinical trials have been reported in patients with advanced refractory urothelial carcinoma, showing remarkable tumor shrinkage by conventional radiologic assessment. One of the trials was using MPDL3280 and another one using pembrolizumab. The response rate with both of these agents is about 25% in heavily pretreated urothelial cancer patients. These two studies demonstrating that bladder cancer is responsive to checkpoint inhibition are the foundation for the ongoing efforts to develop these therapies in this disease.

Cancer Network: What data are you looking forward to in 2015 as it relates to urothelial cancer advances?

Dr. Apolo: I am looking forward to the update of the TCGA data in the planned 500 tumors that will be analyzed, because previously they had reported on only 131 tumors.

I am also looking forward to the initiation of several precision medicine–designed clinical trials, including a maintenance study in Europe and a cooperative group study in the United States for refractory urothelial carcinoma that harbors certain alterations.

In terms of immunotherapy data, I am looking forward to longer follow-up data of the immunotherapy trials in metastatic urothelial carcinoma patients. There are currently two phase III trials that have been initiated using checkpoint inhibitors in advanced urothelial carcinoma using MPDL3280 and pembrolizumab, and many combination trials of checkpoint inhibitors with other checkpoint inhibitors, radiation therapy, or targeted therapy in urothelial carcinoma patients. It seems that combination therapy may be the answer to higher responses because, potentially, it increases T-cell infiltration into the tumor, therefore priming the tumor for better response to checkpoint inhibition.

It is a very exciting time to be working in bladder cancer. Over the last decade, bladder cancer trials have yielded one disappointment after the other, but I feel that we are in a new era and this will be the decade of paradigm shift in bladder cancer.

Cancer Network: Great. Thanks for providing this excellent overview of the current state of bladder cancer treatment.

Dr. Apolo: My pleasure. Thank you so much for having me.