Treatment Options for Bladder Cancer: What's New and What's Next

The treatment paradigm for bladder cancer has been quite exciting in the last few years, and even more is yet to come, according to Petros Grivas, M.D., Ph.D.

“It’s really an exciting time in bladder cancer and urothelial cancer in general. The updates we are seeing in immunotherapy in this disease have transformed the way we treat urothelial cancer over the last few years, specifically in the metastatic urothelial cancer space,” he said in an interview with OncLive, a sister publication of CURE’s.

At the 33^rd annual Society for Immunotherapy of Cancer (SITC) Meeting, Grivas — who is an oncologist at Seattle Cancer Care Alliance, clinical director of the Genitourinary Cancers Program and an associate professor at the University of Washington – discussed what’s new and what’s next in immunotherapy for bladder cancer.

You just gave a presentation on immunotherapy in bladder cancer. Can you start by giving us a short overview of your presentation, with some of the key points?

We tend to have patients who get treatment with platinum-based chemotherapy. But if these patients progress after or during that therapy, now we have five immune checkpoint inhibitors that have been approved by the Food and Drug Administration (FDA) in the platinum-refractory advanced urothelial cancer setting. One of them met the primary endpoints of overall survival when compared to chemotherapy in a phase 3 trial, with a high level of evidence in that space, while the other four checkpoint inhibitors are also approved as options.

In the frontline setting, again in metastatic advanced urothelial cancer, if someone cannot take cisplatin because of medical comorbidities or performance status, we have two checkpoint inhibitors approved in that space Keytruda (pembrolizumab) and Tecentriq (atezolizumab) based on single-arm phase 2 studies.

There are also Food and Drug Administration (FDA)-approved options that have changed the way that we treat urothelial cancer compared to prior years and we now have emerging data on the use of these checkpoint inhibitors earlier in the disease course.

In the non-muscle invasive disease setting and the neo-adjuvant muscle-invasive disease setting, the data is not practice-changing yet, but are very promising and support further evaluation of checkpoint inhibitor therapy in earlier disease settings.

Moreover, we have a lot of clinical trials with combinations — looking at checkpoint inhibition plus other agents – that are very important. The take home point is that we have to support and accrue for these clinical trials in order to identify new therapies, and also potentially prognostic and predictive biomarkers, hopefully with clinical utility down the road that can help identify the right treatment for the right patient at the right time.

Do you think that chemotherapy is here to stay, or do you think that perhaps immunotherapy could replace it?

I think chemotherapy is here to stay and there are and will be many patients who benefit from it, but I think right now we have a one size fits all approach because we don’t have many predictive biomarkers for our patient population.

However, I think in the future, we may have a more sophisticated approach with more precision medicine and more personalized medicine where we can hopefully use biomarkers to identify the right treatment for the right patient.

Some patients may benefit from chemotherapy more than other therapies, or maybe just one part of the treatment paradigm, and we have to identify the better sequence. Do we start with chemotherapy and follow with immunotherapy or vice versa? Or do we use a combination? I think this is all going to be defined in the next few years. But I think that chemotherapy will have some role in the overall change in the treatment paradigm for urothelial cancer.

You mentioned some ongoing trials with immunotherapy and other agents. Can you highlight one or two of these other agents?

We have antibody drug conjugates — we heard about data involving at least two of them, enfortumab vedotin and sacituzumab govitecan – which are being evaluated in clinical trials in patients with advanced urothelial cancer. We also have single agents in combination with immune checkpoint inhibitors, and vaccines that we are evaluating in combination with checkpoint inhibitors. Trials looking at those vaccines are very exciting and worth accruing in the first- and second-line setting.

There are also trials involving targeted therapies. We heard about data on FGF receptor inhibitors in clinical trials. There are also clinical trials investigating PARP inhibitors that are looking very promising either as single agents or combined with checkpoint inhibitors, as well as other targeted therapies against EGFR or HER2. They are also investigating other checkpoint inhibitors in combination, chemotherapy/immunotherapy combinations, and some trials even look at radiation therapy with checkpoint inhibition.

There is a plethora of different mechanisms and biomarkers that are being investigated currently that are all very interesting.