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When to Start Systemic Treatment in Newly Diagnosed RCC

Panelists:Robert A. Figlin, MD, FACP, Cedars-Sinai Medical Center;Daniel J. George, MD, Duke University Medical Center;Thomas Hutson, DO, PharmD, Baylor Charles A. Sammons Cancer Center;David F. McDermott, MD, Dana Farber Harvard Cancer Center;Elizabeth R. Plimack, MD, MS, Fox Chase Cancer Center;Nizar M. Tannir, MD, FACP, MD Anderson Cancer Center
Published: Wednesday, Jun 29, 2016


Transcript:

Robert A. Figlin, MD:
Hello, and thank you for joining us today for this OncLive Peer Exchange Panel Discussion on the topic of advanced renal cell carcinoma sequencing therapies. As progress in the field of renal cell carcinoma research continues to generate new therapies and longer survivals, we are faced with new opportunities and challenges with respect to optimizing treatment for each patient with this advanced disease. In this OncLive Peer Exchange, a panel of experts will discuss the latest information on how to incorporate and sequence novel agents as part of an individualized therapeutic approach.

My name is Dr. Robert Figlin, and I’m a Steven Spielberg Family Chair in Hematology/Oncology, professor of medicine and biomedical sciences, director for the Division of Hematology/Oncology, and deputy director of the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, in Los Angeles, California. Participating today on our distinguished panel are Dr. Daniel George, professor of medicine and surgery and the director of genitourinary oncology at Duke University Medical Center in Durham, North Carolina; Dr. Thomas Hutson, professor of medicine and director of the Genitourinary Oncology Program at the Baylor Sammons Cancer Center in Dallas, Texas; Dr. David McDermott, associate professor in the Department of Medicine at Harvard Medical School, staff physician of hematology/oncology at Beth Israel Deaconess Medical Center, and leader of the Kidney Cancer Program at the Dana-Farber/Harvard Cancer Center in Boston, Massachusetts; Dr. Elizabeth Plimack, director of genitourinary clinical research and associate professor in the Department of Hematology/Oncology at Fox Chase Cancer Center/Temple Health in Philadelphia, Pennsylvania; and Dr. Nizar Tannir, professor and deputy chairman in the Department of Genitourinary Medical Oncology at the University of Texas MD Anderson Cancer Center in Houston, Texas. Thank you, so much, for joining us today. Let’s begin.

So, Elizabeth, let’s start with you, and just set the stage. Patients oftentimes present with a kidney cancer, whether it’s early stage or later-stage disease. And one of the things that our colleagues would like to know is what you think is the role of biopsying that mass if a person’s definitely going to go to surgery. So help us understand the role of biopsying a primary mass in RCC.

Elizabeth R. Plimack, MD, MS: I think the key distinction is whether they have metastatic disease radiographically or not. Certainly, if they don’t, we want to optimize their chance for cure. And there, if the lesion meets radiographic criteria, often we don’t need a biopsy. The lesion really should come out in order to determine what it is and give the patient the best chance. So, in that setting, I think it’s more straightforward. In the setting of metastatic disease, it’s been our convention to perform cytoreductive nephrectomy to remove the primary lesion and then start systemic therapy. I think that’s based on old data that showed a survival benefit to that approach. We don’t know if that’s true now, but I would argue that going for surgery and skipping the biopsy gives a couple of advantages. One is we get true pathology from it; biopsies can be non-diagnostic or discordant. And the other is that it spares a patient any local symptoms from that mass that may come on down the road and cause problems.

Robert A. Figlin, MD: Let’s extend that a little bit and say we have a newly diagnosed patient with advanced disease. It’s biopsied, and we know that it’s kidney cancer. We’ll talk more about the heterogeneous types of kidney cancer in a future discussion. How do you decide when to begin therapy, and what goes through your mind when the patient’s in front of you and you are faced with metastatic disease in an untreated patient, helping to make a decision about start now versus start later? How do you think about that?

Elizabeth R. Plimack, MD, MS: I think the key is if you have the opportunity to really try to judge the pace of their disease. Either look back at old scans to see how their disease has evolved or, if their initial diagnostic scan was older—and often it is—just get another one right before you start. We have patients where we’ve been set up to start treatment. We get that scan, and the disease is stable; those patients can enjoy a period of time off of treatment without any side effects from treatment. I think the caveat is if you have a patient who’s symptomatic from their disease; if they have a lesion in a location that’s threatening a critical structure or organ, those are the people you’re going to want to start sooner. And then it’s also patient discussion. Some people really just want to be on treatment; some wish to avoid it for as long as possible.

Robert A. Figlin, MD: Just in a ballpark, what percentage of your patients do you think, over the course of a year, you actually watch for a period of time before initiating systemic therapy?

Elizabeth R. Plimack, MD, MS: We actually looked at that as part of a clinical trial, and I would say it ended up being about 10%. It’s generally a lot of patient/physician selection bias and gestalt, but yes, it’s about 10% who can get away without treatment.

Robert A. Figlin, MD: Dan, some thoughts?

Daniel J. George, MD: Yes. You know, I think this is a really interesting area because this isn’t represented in our clinical trial population. For the most part, most of our trial data that we have, and that we base a lot of our information on, is patients who are starting on systemic therapy. So, this space, before starting systemic therapies, is somewhat uncharted. We’ve actually looked in a context of a prospective registry, and it actually turns out to be about 25%.

Elizabeth R. Plimack, MD, MS: Right.

Daniel J. George, MD: One of the interesting things I think is coming out of that is predictors for this, and it seems to be volume of disease. So, in addition, I would say patients with really low-volume disease are the other ones—and you guys can chime in. These are the patients for whom you look at little tiny lung nodules and ask, “Hey, can we wait a few months, look at them, and consider maybe a delayed therapy approach?”

Elizabeth R. Plimack, MD, MS: Right. And those are the lesions that tend to be less symptomatic and less threatening.

Robert A. Figlin, MD: So David, one question for you: do we risk them benefiting from therapy by waiting?

David F. McDermott, MD: As far as I know, there’s no evidence of that; meaning, I think patients with symptoms may do worse, but as long as you’re intervening before that develops, they should do just as well with most of these treatments. It’s a hard conversation, though, to have—as Betsy was saying—with patients. Particularly when they get to you, they’re often anxious, motivated to do something: “Why aren’t you going to do something, doctor?” But, to me, what I try to explain is that for many of these treatments, they’ll help you live meaningfully longer on treatment, but they almost always eventually stop working. In individual patients, we don’t know when that’s going to be, but the sooner we start, the sooner we get to the point where we’re going to need to do something else. So, I try to tell them, “If we wait to start, that puts off the time where we’re going to need to do the next thing,” and that gets many people to agree—but it’s not for everyone.

Transcript Edited for Clarity
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Transcript:

Robert A. Figlin, MD:
Hello, and thank you for joining us today for this OncLive Peer Exchange Panel Discussion on the topic of advanced renal cell carcinoma sequencing therapies. As progress in the field of renal cell carcinoma research continues to generate new therapies and longer survivals, we are faced with new opportunities and challenges with respect to optimizing treatment for each patient with this advanced disease. In this OncLive Peer Exchange, a panel of experts will discuss the latest information on how to incorporate and sequence novel agents as part of an individualized therapeutic approach.

My name is Dr. Robert Figlin, and I’m a Steven Spielberg Family Chair in Hematology/Oncology, professor of medicine and biomedical sciences, director for the Division of Hematology/Oncology, and deputy director of the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, in Los Angeles, California. Participating today on our distinguished panel are Dr. Daniel George, professor of medicine and surgery and the director of genitourinary oncology at Duke University Medical Center in Durham, North Carolina; Dr. Thomas Hutson, professor of medicine and director of the Genitourinary Oncology Program at the Baylor Sammons Cancer Center in Dallas, Texas; Dr. David McDermott, associate professor in the Department of Medicine at Harvard Medical School, staff physician of hematology/oncology at Beth Israel Deaconess Medical Center, and leader of the Kidney Cancer Program at the Dana-Farber/Harvard Cancer Center in Boston, Massachusetts; Dr. Elizabeth Plimack, director of genitourinary clinical research and associate professor in the Department of Hematology/Oncology at Fox Chase Cancer Center/Temple Health in Philadelphia, Pennsylvania; and Dr. Nizar Tannir, professor and deputy chairman in the Department of Genitourinary Medical Oncology at the University of Texas MD Anderson Cancer Center in Houston, Texas. Thank you, so much, for joining us today. Let’s begin.

So, Elizabeth, let’s start with you, and just set the stage. Patients oftentimes present with a kidney cancer, whether it’s early stage or later-stage disease. And one of the things that our colleagues would like to know is what you think is the role of biopsying that mass if a person’s definitely going to go to surgery. So help us understand the role of biopsying a primary mass in RCC.

Elizabeth R. Plimack, MD, MS: I think the key distinction is whether they have metastatic disease radiographically or not. Certainly, if they don’t, we want to optimize their chance for cure. And there, if the lesion meets radiographic criteria, often we don’t need a biopsy. The lesion really should come out in order to determine what it is and give the patient the best chance. So, in that setting, I think it’s more straightforward. In the setting of metastatic disease, it’s been our convention to perform cytoreductive nephrectomy to remove the primary lesion and then start systemic therapy. I think that’s based on old data that showed a survival benefit to that approach. We don’t know if that’s true now, but I would argue that going for surgery and skipping the biopsy gives a couple of advantages. One is we get true pathology from it; biopsies can be non-diagnostic or discordant. And the other is that it spares a patient any local symptoms from that mass that may come on down the road and cause problems.

Robert A. Figlin, MD: Let’s extend that a little bit and say we have a newly diagnosed patient with advanced disease. It’s biopsied, and we know that it’s kidney cancer. We’ll talk more about the heterogeneous types of kidney cancer in a future discussion. How do you decide when to begin therapy, and what goes through your mind when the patient’s in front of you and you are faced with metastatic disease in an untreated patient, helping to make a decision about start now versus start later? How do you think about that?

Elizabeth R. Plimack, MD, MS: I think the key is if you have the opportunity to really try to judge the pace of their disease. Either look back at old scans to see how their disease has evolved or, if their initial diagnostic scan was older—and often it is—just get another one right before you start. We have patients where we’ve been set up to start treatment. We get that scan, and the disease is stable; those patients can enjoy a period of time off of treatment without any side effects from treatment. I think the caveat is if you have a patient who’s symptomatic from their disease; if they have a lesion in a location that’s threatening a critical structure or organ, those are the people you’re going to want to start sooner. And then it’s also patient discussion. Some people really just want to be on treatment; some wish to avoid it for as long as possible.

Robert A. Figlin, MD: Just in a ballpark, what percentage of your patients do you think, over the course of a year, you actually watch for a period of time before initiating systemic therapy?

Elizabeth R. Plimack, MD, MS: We actually looked at that as part of a clinical trial, and I would say it ended up being about 10%. It’s generally a lot of patient/physician selection bias and gestalt, but yes, it’s about 10% who can get away without treatment.

Robert A. Figlin, MD: Dan, some thoughts?

Daniel J. George, MD: Yes. You know, I think this is a really interesting area because this isn’t represented in our clinical trial population. For the most part, most of our trial data that we have, and that we base a lot of our information on, is patients who are starting on systemic therapy. So, this space, before starting systemic therapies, is somewhat uncharted. We’ve actually looked in a context of a prospective registry, and it actually turns out to be about 25%.

Elizabeth R. Plimack, MD, MS: Right.

Daniel J. George, MD: One of the interesting things I think is coming out of that is predictors for this, and it seems to be volume of disease. So, in addition, I would say patients with really low-volume disease are the other ones—and you guys can chime in. These are the patients for whom you look at little tiny lung nodules and ask, “Hey, can we wait a few months, look at them, and consider maybe a delayed therapy approach?”

Elizabeth R. Plimack, MD, MS: Right. And those are the lesions that tend to be less symptomatic and less threatening.

Robert A. Figlin, MD: So David, one question for you: do we risk them benefiting from therapy by waiting?

David F. McDermott, MD: As far as I know, there’s no evidence of that; meaning, I think patients with symptoms may do worse, but as long as you’re intervening before that develops, they should do just as well with most of these treatments. It’s a hard conversation, though, to have—as Betsy was saying—with patients. Particularly when they get to you, they’re often anxious, motivated to do something: “Why aren’t you going to do something, doctor?” But, to me, what I try to explain is that for many of these treatments, they’ll help you live meaningfully longer on treatment, but they almost always eventually stop working. In individual patients, we don’t know when that’s going to be, but the sooner we start, the sooner we get to the point where we’re going to need to do something else. So, I try to tell them, “If we wait to start, that puts off the time where we’re going to need to do the next thing,” and that gets many people to agree—but it’s not for everyone.

Transcript Edited for Clarity
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