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Immunotherapy Advances Again Propel Progress in GU Malignancies

Gina Columbus @ginacolumbusonc
Published: Thursday, Aug 11, 2016

Randy F. Sweis, MD

Randy F. Sweis, MD

Across the fields of renal cell carcinoma (RCC), bladder cancer, and prostate cancer, immunotherapy agents are moving through the pipeline and impacting patient outcomes—some quicker than others.

“Now, we see that anti–PD-1 therapy has taken off,” explains Randy F. Sweis, MD. “Suddenly, GU has come at the forefront of immunotherapy again and we are all excited about that.”

Sweis, who gave a lecture on bone-targeting agents in prostate cancer during the 2016 OncLive State of the Science Summit on GU and Prostate Cancer, has a keen research interest in immunotherapy in GU malignancies—and understanding why some patients are resistant to them.

In an interview with OncLive during the meeting, Sweis, a clinical instructor at the University of Chicago Medicine, covers the immunotherapy advancements in prostate cancer, RCC, and bladder cancer, and what refinement lies ahead in each of these areas.

OncLive: How have you seen an evolution toward immunotherapy in GU cancers?

Sweis: GU cancers have had an interesting historical course, where initially, BCG [bacillus Calmette-Guérin], which is an immunotherapy instilled intravesically in the bladder, was the second immunotherapy ever approved by the FDA. That occurred after interferon-alpha, so it was at the forefront of immunotherapy.

Then, there was sort of a lull where, for decades, we did not have much—especially in bladder cancer. In RCC, we saw the development of the tyrosine kinase inhibitors and, in prostate cancer, we saw a lot of secondary androgen-targeted agents. However, bladder cancer sort of remained with no new FDA-approved drugs until atezolizumab (Tecentriq). Therefore, it is an exciting time.

Can you discuss the IMvigor 210 study, and how those results led to the FDA approval?

In IMvigor 210, we saw a lot of interesting durability to the responses, and I think that is what people are most excited about. My research interest is understanding resistance mechanisms, and although we are all excited about the responses we saw, the response rate is still not where we want it, especially in PD-L1–negative patients. There is definitely a subset of patients who are not having the responses we want.

Overall, when taking all comers with bladder cancer, there are probably one-quarter of patients who will have a response to PD-1, which is shown on the survival curves. There is impressive durability—sort of the tail on the curve that is noted at the end—but the majority of patients are still having disease progression, which is where there will be a lot of work going forward. To temper some of the excitement about the approval, there is still a lot of work to be done.

What clinical trials should be done in an effort to get more patients responding to therapies?

A lot of this is already happening. I have recently heard of as many as 500 different clinical trials where there are combinations of PD-1 targeted therapy with other agents. Results will likely rely heavily on some preclinical data and the understanding of immune biology—and that is critical. There are a lot of drugs that are active.

Chemotherapies are active still, so we are looking at potentially combining immunotherapies with chemotherapies. Radiation, of course, is of interest. We have a phase I study in our Developmental Therapeutics Program combining radiation with an anti–PD-1 drug. We also have targeted therapies.

In RCC, we have had many targeted tyrosine kinase inhibitors that have been approved in the past decade. How do they fit in with immunotherapy? These are questions that are ongoing and we are going to learn a lot in the next decade.

How is the FDA approval of atezolizumab going to shake up the treatment landscape of bladder cancer?

It is going to be a dramatic change. It has been a difficult discussion in clinic for patients who have had no response or had a response, but had had a recurrence to chemotherapy. We do not have many therapeutic options to offer that are highly effective and minimally toxic, and this is now one of them. It is very exciting for a patient who is sick, but still has a good performance status, and is eager to get some kind of treatment for their disease, and there was previously not much else to give them. This new approval will offer something different and will be more widely available outside of clinical trials, now that we have it FDA approved.

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