Potential for Neoadjuvant Immunotherapy in Bladder Cancer Is Wide Open, Expert Says

Geoffrey Sklar, MD

With immunotherapy agents such as nivolumab (Opdivo) showing significant promise in bladder cancer, the potential for these agents in the neoadjuvant setting is wide open, says Geoffrey Sklar, MD, Chief Medical Officer of Chesapeake Urology Associates.

In an interview with OncLive during the 2016 LUGPA Annual Meeting, Sklar discussed the need for better treatments for non-muscle invasive bladder cancer, the promise of nivolumab, and challenges he would still like to see tackled in the field.

OncLive: Can you discuss some of the recent advancements with immunotherapy in bladder cancer?

Sklar: Right now, the buzz is the PD-L1 inhibitor drugs that have come out that are approved for urothelial carcinoma and renal cell carcinoma (RCC), as well as other malignancies, but for advanced disease. The bigger buzz, or additional buzz, is does this have a role in early disease as a neoadjuvant, or even for non-muscle invasive bladder cancer?

I think people have already heard about the possible uses in advanced metastatic disease, but those other areas, particularly the high-grade, non-invasive bladder cancers, are sort of an enigma for us. We don’t really have great therapies for them, and the goal is to see whether there is a place for them to fit into that paradigm.

What are your thoughts on the success nivolumab is showing, and what impact could that immunotherapy agent have if it is approved by the FDA?

I don’t have any personal experience with nivolumab, but the data for bladder cancer and advanced disease shows significant improvement over what we have currently, which is platinum-based chemotherapy—cisplatin/gemcitabine is sort of the gold standard at this point.

These are the worst of the worst patients that are currently getting these medications, they’ve usually failed either neoadjuvant or adjuvant therapies, and we are seeing some responders with immunotherapy.

I think for the future, particularly for patients who have had very little or no hope, now there is at least hope that these agents may work in some of these patients. It’s not clear who it will work with right now—I think that is one of the other things we need to look forward to when we can actually figure out who will respond to these immunotherapies and who will not, and who we shouldn’t waste time with chemotherapy on.

How do you decide which patients nivolumab might work best with?

Currently, we’re sort of using it in advanced patients, patients who have had cystectomy with nodal disease or metastatic disease and either failed therapy or are not candidates for frontline therapy. But I think in the future we’re going to be looking at much different ways of potentially even intravesical therapies with these drugs—they’re not FDA approved for that—but the space for neoadjuvant therapy with these types of drugs is wide open.

The space even in the non-muscle invasive population is of interest. Whether the side effect profile works for the patients with non-muscle invasive bladder cancer will sort of pan out over time. Right now there’s potential, we just don’t know which spaces of bladder cancer these drugs will work best in. Right now I think everybody is excited about every stage of bladder cancer.

Is there any ongoing immunotherapy research in bladder cancer that you are excited to see the results from?

I think right now the trials are in their infancy. The problem with bladder cancer is it’s very hard to do uniform trials. Getting people all at the same stage—the patients with the advanced disease are usually older, 70s and 80s, may have been their second cancer, maybe relatively sick patients.

My personal thought is to see if we can get these earlier. The data for prostate cancer, now I realize they are totally different drugs and a totally different approach, but the immunotherapy tends to work best with low volume disease getting it earlier. That would be my hope as well for bladder cancer.

What are some of the challenges in the field of bladder cancer that you would still like to see tackled?

The BCG-refractory carcinoma in situ group is a very progressive, deadly disease when you don’t respond to BCG and many times we delay and give them alternative intravesical therapies for months if not a year and still about a third of the patients will actually succumb to their disease. That’s the one area I think is still open for a major improvement in our care.

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