2016 ASCO Annual Meeting Research Round Up – Bladder Cancer and Kidney Cancer, with Brian Rini, MD

July 28, 2016
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In today’s podcast, Lineagotica Associate Editor Dr. Brian Rini discusses some of the new research on kidney and bladder cancer presented at the 2016 ASCO Annual Meeting.



ASCO: You're listening to a podcast from Lineagotica. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world's leading professional organization for doctors that care for people with cancer.

In today's podcast, Lineagotica Associate Editor Dr. Brian Rini discusses some of the new research on kidney and bladder cancer presented at the 2016 ASCO Annual Meeting. Dr. Rini is a professor of medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University and a staff member of the Department of Solid Tumor Oncology at Cleveland Clinic Taussig Cancer Institute. The ASCO Annual Meeting is the premier educational and scientific event where physicians, researchers, and other healthcare professionals gather to discuss the latest in cancer care and treatment. This Lineagotica podcast helps put new research findings into context and explains what they mean for patients. ASCO would like to thank Dr. Rini for summarizing this research.

Dr. Rini: Hi, this is Brian Rini from the Cleveland Clinic Taussig Cancer Center. And I'm going to talk to you about some exciting developments in the arena of advanced bladder cancer, and also advanced kidney cancer. As you may know, a lot of developments in cancer recently have involved immune checkpoint inhibitors. And certainly, kidney and bladder cancer are no exception to this. So just to explain briefly, when we talk about these "checkpoint inhibitors," the way I explain it to patients is that, in essence, they are treatments that remove the breaks on the immune system. We all have natural cells in our body and mechanisms to dampen immune responses. Otherwise, we'd all have bad autoimmune diseases. Patients with advanced cancer, presumably, their immune system is trying to fight the cancer but obviously not doing a good job. And so, the idea of these drugs is to remove the breaks on the immune system and allow people's natural anti-tumor immunity to come through. And certainly, these drugs are being developed widely across many cancers and are now FDA approved in many cancers.

And there's been some exciting new data, specifically in bladder cancer, that I'd like to talk to you about, presented at this year's ASCO Annual Meeting. So the first set of abstracts, again, was about a variety of these checkpoint inhibitors in bladder cancer. Just weeks before the Annual Meeting, a drug called atezolizumab, which goes by the brand name of Tecentriq, was approved in advanced bladder cancer patients who had already been treated with a chemotherapy drug called cisplatin, which is a standard agent in this disease. And that FDA approval was on the basis of a response rate, meaning patient's tumor shrinking. It also appeared that patients whose tumors expressed a certain protein called PD-L1, who's immune cells around the tumor expressed this protein, had a slightly better response. Unfortunately, bladder cancer hasn't had any sort of developments or drug approval in at least two decades and so this was certainly welcome news for patients and physicians alike.

Building on this, then at ASCO 2016, there were a number of updates to the data with atezolizumab as well as other drugs. And basically, what was presented was again an update of that drug - atezolizumab - in patients who had already gotten cisplatin as well as a separate dataset of patients who were not eligible to receive cisplatin. So cisplatin is a very difficult drug to receive. It causes nausea and vomiting. It can be very difficult on patients' kidney function. Patients with bladder cancer are often older, have other health conditions, and often have decreased kidney function for a variety of reasons. So some of them aren't even eligible to get what we would consider standard therapy. And in these patients who received atezolizumab - this checkpoint inhibitor - they also had very impressive response rates - rates of tumor shrinking - providing another option for these patients aside from chemotherapy. Right now, the drug is only approved in patients who've received prior chemotherapy, but I think that it's likely that they'll be other approvals of this drug in different settings. And there are also large, randomized trials going on to more precisely define the role of this drug. But I think it's pretty clear that this drug will have a major role on how we approach bladder cancer both before and after chemotherapy or in replacement of chemotherapy.

There were a couple other similar checkpoint inhibitors in bladder cancer. One called durvalumab which is made by AstraZeneca/MedImmune. A drug called nivolumab which is approved in some other diseases made by BMS. And basically, all of these abstract were in patients with advanced bladder cancer, many of them in patient who had gotten a prior chemotherapy which is standard. And although there were different numbers for response rates, I think they all show that there's clear activity to this approach for this population of patients in shrinking tumors. They all looked at different biomarkers, which are markers we try to use to predict who might respond. And I think it's some fairly early data, but as with the atezolizumab, it appears that patients whose tumors express this PD-L1 on their tumor cells and or on their immune cells seem to have a higher response rate. Right now, atezolizumab and these other drugs have been used in all patients. But it may be that we refine how we give these drugs and to whom we give these drugs moving forward. And I think it's expected that more than just the one drug in the one setting will receive FDA approval in the next 12 to 18 months. But there's a lot of activity, again in an area that hasn't seen advances in at least two decades. So I think that was, for me, one of the most exciting developments in genitourinary cancers, certainly in bladder cancer, that we've seen in a long time.

I think the other major advances in data that were seen were in the arena of advanced kidney cancer. Kidney cancer has had a lot of advances over the last decade, unlike bladder cancer, with so-called targeted therapy. In kidney cancer targeted therapy means therapy targeted against blood vessels. And it has to do with the inherent biology of the disease, which produces factors which stimulate blood vessel growth and feed the tumor and allow it to grow and spread. And many drugs have been FDA approved over the last decade that attack this mechanism. These drugs are called, sometimes, TKI's or VEGF inhibitors. There was an update of a large trial involving a drug called cabozantinib. Cabozantinib is a drug that was also recently approved for advanced kidney cancer on the basis of the trial, which showed advantages over a drug called everolimus or Afinitor. The latter drug has been a standard in refractory kidney cancer for quite some time. And cabozantinib is not only an anti-blood vessel drug, but it inhibits some other proteins as well, which is postulated to give it some advantages clinically.

And so, there was an update of this trial, which already resulted in FDA approval but the update had to do with overall survival. And that patients who receive this drug compared to patients who received the older everolimus drug, live longer. And so I think it's really sort of pushing the boundaries of targeted therapy and kidney cancer. Although, we've had drugs that have been approved for over ten years and in clinical trials probably for over 15 years, we're still finding new drugs that target different pathways. The same pathways and additional pathways to provide benefit for patients. And so, I think we're really squeezing all we can out of targeted therapy. And this drug, again, is approved in refractory patients. There's also some data - not presented in ASCO, but will be presented soon - of using this drug as initial therapy. So just when we thought we plateaued with targeted therapy, along comes this drug and really provides some clinical benefits. There can be substantial toxicity with this drug, like many of the targeted therapies, and so, it's incumbent upon the physicians to learn how to use this drug best, and what dose, and what patients, and all the things that we think about when we're applying drugs to patients.

And then, lastly, in kidney cancer. I mentioned the explosion of checkpoint inhibitors in bladder cancer, and kidney cancer as well that has happened. There's a drug that I mentioned in bladder, called nivolumab which is one of these checkpoint inhibitor immunotherapy anti-bodies. And that drug, actually, was approved in kidney cancer late in 2015 on the basis of a trial showing advantages also over that everolimus that I mentioned from the previous trial. So it was FDA approved and is now in common use. What was interesting at ASCO, is that Dave McDermott from Beth Israel who's a Medical Oncologist and active in kidney cancer presented some long-term data of this drug in patients with kidney cancer who were from the early studies. The phase one and two studies, which are generally early safety studies before a drug is FDA approved. And he provided some updated data on a relatively small number of patients - just over a hundred - but patients who had been on this drug for many years. One of the exciting aspects of immunotherapy is that, unlike I think, most targeted therapy - at least in kidney cancer - is that there's the potential for long-term disease control. We don't know if patients will be cured with this therapy yet because it requires many years to study that. But we do know that some patients, a subset of patients, can have very long-term disease control and really not need another therapy for many years, and tolerate the immune therapy quite well.

The data that was presented at ASCO, this year suggested data from at least these early phase trials, that it was about 20 or 30% of patients who were alive and doing well either on or off drug over four years later. So that can be quite a long time for patients with advanced kidney cancer. Preliminary data patients who get on these trials are very selected. They're often healthier than your average patient so to speak. But, nonetheless, I think it's exciting to know that there may be an opportunity for long-term survival - at least in a subset of patients - with this therapy. And it didn't appear to be any more toxic over time. So we need more data and longer follow-up on these patients and patients from the randomized trials to really know. But I think as a physician selecting therapy, one of the things you think about is, "Can I keep this patient on therapy and control their disease for a long time without side-effects?" I think that's a goal for all of us who treat patients for a living and I think these are some early data's to suggest that this drug may have that possibility. Unfortunately, not in all patients, but I think in a reasonably substantial minority of patients.

And then the hope, of course, is to build on this by either adding other drugs or finding biomarkers to know who those patients are upfront, and that's an area of intense ongoing research. So we look forward to more data and there are a number of drugs like nivolumab, being studied in combination with some of the targeted therapy I mentioned. And those are very large trials that we'll read out over the next few years and I think, are likely to change our approach to the disease. So, in summary, ASCO 2016 for kidney and bladder cancer was, much like other cancers, was a lot of immunotherapy, a lot of these checkpoint inhibitors - specifically in bladder cancer - coming on the heels of atezolizumab FDA approval and many more drugs coming to expand options in this disease that desperately needs more options. And as well, some updates in kidney cancer with some long-term follow-up of immunotherapy and also new targeted therapy such as cabozantinib which is entering the treatment arena. Thank you for your attention.

ASCO: Thank you, Dr. Rini. To learn more about the science presented at the 2016 ASCO Annual Meeting, visit lineagotica.info/ascoannualmeeting. If you have questions about whether new research may affect your care, be sure to talk with your doctor.

Lineagotica is supported by the Conquer Cancer Foundation, which is working to create a world free from the fear of cancer by funding breakthrough research, sharing knowledge with physicians and patients worldwide, and supporting initiatives to ensure that all people have access to high-quality cancer care. Thank you for listening to this Lineagotica podcast.