Past, Present and Future: 'Immunotherapy is Here to Stay'

Following the approval of five agents in the bladder cancer space a few years ago, immunotherapy as a treatment option for the disease is here to stay, according to Arjun V. Balar, M.D.

At the 2019 Genitourinary Cancers Symposium, Balar — who is director of the genitourinary medical oncology program at NYU Langone’s Perlmutter Cancer Center – sat down with OncLive, a sister publication of CURE’s, to discuss the past, present and future of immunotherapy for the treatment of bladder cancer.

OncLive: In terms of biomarkers, where do we stand right now?

Balar: In bladder cancer, and certainly metastatic disease, I think there has been some major advances in terms of biomarkers for select patients who should or should not receive PD-1 antibodies. So, for instance PD-L1 expression certainly has value in the first-line metastatic setting. In high-risk non-muscle invasive bladder cancer, I (presented) data regarding the role of PD-L1 expression. Interestingly, we find that PD-L1 expression does not really predict the rates of (complete response) in patients with non-muscle invasive bladder cancer; however, other biomarkers are needed to be tested, certainly in metastatic disease. Another thing worth looking at is tumor mutational burden, but that is currently in development. However, in non-muscle invasive disease, the field is too early.

Are there any other updates presented at ASCO GU that you’re excited about?

What I’m particularly excited about in bladder cancer is what Scott T. Tagawa, M.D., MS, (from Weill Cornell Medicine) will be presenting, which is data from the phase 1 study of IMMU-132, which is sacituzumab govitecan, an antibody drug conjugate. It is particularly important for patients who are not responsive to PD-1 antibodies. We know that about 20 percent of patients with respond in the second-line setting to immunotherapy, and that means for the remaining large portion of patients, we need treatment options for them. It seems that antibody drug conjugates are quite attractive in terms of inducing responses and achieving disease control. So, I am quite excited about seeing that data.

If we can work out the challenges with immunotherapy, what are the next steps?

Immunotherapy in bladder cancer is here to stay. I think it will be firmly established even as a part of first-line therapy. Keynote-361 and IMvigor130, these are two randomized phase 3 trials that are testing platinum chemotherapy alone, immunotherapy alone versus platinum-based chemotherapy and immunotherapy. I think any of us in the field feel and anticipate that platinum chemotherapy plus immunotherapy will be a new standard of care for patients in the first-line setting. However, even for patients who are not eligible for any chemotherapy, immunotherapy will still also have a role because we know that for the majority of patients who can’t tolerate chemotherapy, immunotherapy still remains a viable option.

What is the outlook for patients today compared with five years ago?

The conversations I used to have with patients five or six years ago with metastatic bladder cancer specifically were quite somber. Most instances we were talking about platinum-based chemotherapy, whether we used platinum or carboplatin, then up on progression, single-agent chemotherapy versus best supportive care alone. Many times in the second-line setting, most patients would go for best supportive care because the treatments that we had did not lead to meaningful responses and certainly not an improvement in survival. Now, fast forward to 2019, there are five different agents that target the PD-1 pathway. In the second-line setting we have two agents, in the first-line setting in patients who are cisplatin ineligible, and a number of studies that are evaluating novel compounds have a significant impact, potentially in the near future — these include antibody drug conjugates, immunotherapies that target FGFR3, and others experimental immunotherapy compounds that are quickly reshaping how we treat this disease, how we think about it, and also the long-term outcomes and prognosis of these patients.