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Rapidly Evolving Paradigms for Treating Advanced RCC

Panelists: Robert A. Figlin, MD, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center; Eric Jonasch, MD, University of Texas MD Anderson Cancer Center; Toni K. Choueiri, MD, Dana-Farber Cancer Institute; Michael R. Harrison, MD, Duke Cancer Institute; David I. Quinn, MBBS, PhD, USC Norris Cancer Hospital
Published Online: Monday, Mar 20, 2017



Transcript:

Robert A. Figlin, MD:
Hello, and thank you for joining this OncLive Peer Exchange® titled “The New Frontier: Treating Advanced Kidney Cancer.” Progress over the last decade in the field of renal cell carcinoma has changed the way we treat our patients with advanced disease. As we learn to optimize the use of recently approved therapies, new data continue to emerge to help us navigate a pathway for each individual patient, often through multiple lines of therapy. In this OncLive Peer Exchange®, I am joined by a panel of leaders in the field. We’ll provide practical information on how and when to use available therapies, and how emerging data will apply to clinical practice.

I am Dr. Robert Figlin, and I am the Steven Spielberg Family chair in hematology oncology, professor of medicine and biomedical sciences, director for the Division of Hematology Oncology, and deputy director for the Integrated Oncology Service Line and of the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center in Los Angeles, California. Participating today on our distinguished panel include Dr. Toni Choueiri, director of the Lank Center for Genitourinary Oncology, director of the GU Oncology Disease Center, and attending physician of solid tumor oncology at the Dana-Farber Cancer Institute and associate professor of medicine at Harvard Medical School in Boston, Massachusetts; Dr. Michael Harrison, assistant professor of medicine at Duke Cancer Institute in Durham, North Carolina; Dr. Eric Jonasch, professor of genitourinary medical oncology and co-chair of the Renal Cancer Program at the University of Texas MD Anderson Cancer Center in Houston, Texas; and David Quinn, medical director of USC Norris Cancer Hospital, head of the section of Genitourinary Medical Oncology, and associate professor of medicine in the Division of Oncology at Keck School of Medicine of USC in Los Angeles, California. Thank you for joining us and let’s begin.

Eric, let’s start off by acknowledging that over the last decade, there continues to be an evolving paradigm in the treatment of kidney cancer. Give our audience what you’ve seen over this time period, what’s the shifting paradigm and broad strokes, what are our objectives of treatment when we treat a patient with kidney cancer today, and are there any selection strategies that you might be using when identifying how to approach an individual patient?

Eric Jonasch, MD: Bob, it has actually been a really interesting decade or decade-and-a-half from having only cytokine therapies. We now have molecularly targeted agents against VEGF and VEGF receptors, and more recently, we have immunotherapies that modulate the immune system in very new ways, as well as new targets that we can actually target with targeted agents. So, the question at this point in time is how to use these agents. First of all, it’s pretty clear that we have now prolonged survival. And already with the targeted therapies, we could see that we’ve starting improving overall survival. Now that we have checkpoint antibodies, we’re starting to see a subset of individuals that are starting to get cured. So, I think some of the key questions we want to answer are, what’s the ideal sequence of these agents? It used to be that we would think about sequencing one TKI versus another, but I think now that question really has meat. Do we start with a VEGF-targeted agent? Does that precondition the tumor to then benefit from a checkpoint antibody against PD-1 or PD-L1 more? Do agents like the VEGF receptors and MET and AXL inhibitors like cabozantinib play a role as a chaser after immunotherapy? Should they be used in combination? These are all the questions that we really need to answer.

Right now, we’re doing this in somewhat of an ad hoc fashion. We sequence according to the NCCN guidelines and what insurance companies allow us to do, but what we really need is to understand the underlying biology of the cancer so we can actually predict which drug should be given to which patient at what point in time. We don’t have those tools. We’re going to talk a little bit today about some of the things that are emerging that might lead us in the direction, but it’s going to be, I think, an interesting journey in the next 10 years to redefine how we treat patients.

Robert A. Figlin, MD: Toni, as there are more and more agents for our community physicians to give, often times in centers, like your own center the Lank Center in Boston, the kind of patient that we’re seeing differs now than they did 5 or 10 years ago. Give us a sense of what’s being referred to the major centers, what are the conversations that are taking place when patients are seeing you, and whether that’s changed with the advent of so many options for individuals.

Toni K. Choueiri, MD: Absolutely, Bob. In a way, it’s almost all over the place. What we’ve seen recently is a significant uptake for immuno-oncology (I-O) drugs and PD-1 inhibitors in the community, preceded by the approval of these drugs in other malignancies. So, we’ve seen that. We still see a lot of patients that have been through VEGF tyrosine kinase inhibitors, sometimes for a short period of time, and taken off these drugs without trying to manage the side effects for a longer period of time. We’re seeing, interestingly, a lot of patients that have progressed on multiple, multiple lines of therapies, including I-Os. So, now when we plan clinical trials, we have to be careful about the population that is still sent to us. We still see patients sent for adjuvant therapy, for first-line treatment, but we’re seeing a growing population of patients that progress through all lines of therapies, including immuno-oncology drugs. And this is an unmet need at this time. A lot of our trials in general may not allow for these patients.

Robert A. Figlin, MD: Can I circle back to one of the comments that you made? In our so-called rush to I-O therapies, can you comment whether you think people are getting a fair and full opportunity to benefit from the things that have been around for a decade—the targeted agents against the VEGF receptor in kidney cancer—or is it really that once I see a side effect or an adverse event that the patient doesn’t tolerate, rather than modify the dose in the schedule, I’ll just move on quickly to an I-O?

Toni K. Choueiri, MD: I think you’re spot on. I think initially, once the targeted therapy after 2005 or 2006 being approved, we saw a lot of patients being taken off. And then, several years after, the side effects were managed a bit better. Patients take more. Sometimes I see a patient re-challenged, dose adjusted, and has hypertension and hand-foot skin reaction managed. But since the I-O, I have to be honest with you, I’ve seen the movement going back to where we were. That patient being taken off quickly from agent like sunitinib, pazopanib, sometimes could have stayed for a longer period of time and the side effect could have been managed in a different way.

Transcript Edited for Clarity

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Transcript:

Robert A. Figlin, MD:
Hello, and thank you for joining this OncLive Peer Exchange® titled “The New Frontier: Treating Advanced Kidney Cancer.” Progress over the last decade in the field of renal cell carcinoma has changed the way we treat our patients with advanced disease. As we learn to optimize the use of recently approved therapies, new data continue to emerge to help us navigate a pathway for each individual patient, often through multiple lines of therapy. In this OncLive Peer Exchange®, I am joined by a panel of leaders in the field. We’ll provide practical information on how and when to use available therapies, and how emerging data will apply to clinical practice.

I am Dr. Robert Figlin, and I am the Steven Spielberg Family chair in hematology oncology, professor of medicine and biomedical sciences, director for the Division of Hematology Oncology, and deputy director for the Integrated Oncology Service Line and of the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center in Los Angeles, California. Participating today on our distinguished panel include Dr. Toni Choueiri, director of the Lank Center for Genitourinary Oncology, director of the GU Oncology Disease Center, and attending physician of solid tumor oncology at the Dana-Farber Cancer Institute and associate professor of medicine at Harvard Medical School in Boston, Massachusetts; Dr. Michael Harrison, assistant professor of medicine at Duke Cancer Institute in Durham, North Carolina; Dr. Eric Jonasch, professor of genitourinary medical oncology and co-chair of the Renal Cancer Program at the University of Texas MD Anderson Cancer Center in Houston, Texas; and David Quinn, medical director of USC Norris Cancer Hospital, head of the section of Genitourinary Medical Oncology, and associate professor of medicine in the Division of Oncology at Keck School of Medicine of USC in Los Angeles, California. Thank you for joining us and let’s begin.

Eric, let’s start off by acknowledging that over the last decade, there continues to be an evolving paradigm in the treatment of kidney cancer. Give our audience what you’ve seen over this time period, what’s the shifting paradigm and broad strokes, what are our objectives of treatment when we treat a patient with kidney cancer today, and are there any selection strategies that you might be using when identifying how to approach an individual patient?

Eric Jonasch, MD: Bob, it has actually been a really interesting decade or decade-and-a-half from having only cytokine therapies. We now have molecularly targeted agents against VEGF and VEGF receptors, and more recently, we have immunotherapies that modulate the immune system in very new ways, as well as new targets that we can actually target with targeted agents. So, the question at this point in time is how to use these agents. First of all, it’s pretty clear that we have now prolonged survival. And already with the targeted therapies, we could see that we’ve starting improving overall survival. Now that we have checkpoint antibodies, we’re starting to see a subset of individuals that are starting to get cured. So, I think some of the key questions we want to answer are, what’s the ideal sequence of these agents? It used to be that we would think about sequencing one TKI versus another, but I think now that question really has meat. Do we start with a VEGF-targeted agent? Does that precondition the tumor to then benefit from a checkpoint antibody against PD-1 or PD-L1 more? Do agents like the VEGF receptors and MET and AXL inhibitors like cabozantinib play a role as a chaser after immunotherapy? Should they be used in combination? These are all the questions that we really need to answer.

Right now, we’re doing this in somewhat of an ad hoc fashion. We sequence according to the NCCN guidelines and what insurance companies allow us to do, but what we really need is to understand the underlying biology of the cancer so we can actually predict which drug should be given to which patient at what point in time. We don’t have those tools. We’re going to talk a little bit today about some of the things that are emerging that might lead us in the direction, but it’s going to be, I think, an interesting journey in the next 10 years to redefine how we treat patients.

Robert A. Figlin, MD: Toni, as there are more and more agents for our community physicians to give, often times in centers, like your own center the Lank Center in Boston, the kind of patient that we’re seeing differs now than they did 5 or 10 years ago. Give us a sense of what’s being referred to the major centers, what are the conversations that are taking place when patients are seeing you, and whether that’s changed with the advent of so many options for individuals.

Toni K. Choueiri, MD: Absolutely, Bob. In a way, it’s almost all over the place. What we’ve seen recently is a significant uptake for immuno-oncology (I-O) drugs and PD-1 inhibitors in the community, preceded by the approval of these drugs in other malignancies. So, we’ve seen that. We still see a lot of patients that have been through VEGF tyrosine kinase inhibitors, sometimes for a short period of time, and taken off these drugs without trying to manage the side effects for a longer period of time. We’re seeing, interestingly, a lot of patients that have progressed on multiple, multiple lines of therapies, including I-Os. So, now when we plan clinical trials, we have to be careful about the population that is still sent to us. We still see patients sent for adjuvant therapy, for first-line treatment, but we’re seeing a growing population of patients that progress through all lines of therapies, including immuno-oncology drugs. And this is an unmet need at this time. A lot of our trials in general may not allow for these patients.

Robert A. Figlin, MD: Can I circle back to one of the comments that you made? In our so-called rush to I-O therapies, can you comment whether you think people are getting a fair and full opportunity to benefit from the things that have been around for a decade—the targeted agents against the VEGF receptor in kidney cancer—or is it really that once I see a side effect or an adverse event that the patient doesn’t tolerate, rather than modify the dose in the schedule, I’ll just move on quickly to an I-O?

Toni K. Choueiri, MD: I think you’re spot on. I think initially, once the targeted therapy after 2005 or 2006 being approved, we saw a lot of patients being taken off. And then, several years after, the side effects were managed a bit better. Patients take more. Sometimes I see a patient re-challenged, dose adjusted, and has hypertension and hand-foot skin reaction managed. But since the I-O, I have to be honest with you, I’ve seen the movement going back to where we were. That patient being taken off quickly from agent like sunitinib, pazopanib, sometimes could have stayed for a longer period of time and the side effect could have been managed in a different way.

Transcript Edited for Clarity
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