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Adjuvant Sunitinib's Role in the Treatment of RCC

Panelists: Daniel George, MD, Duke Cancer Institute; Neeraj Agarwal, MD, Huntsman Cancer Institute; Robert Alter, MD, Hackensack University Medical Center; Bradley McGregor, MD, Dana-Farber Cancer Institute; Nicholas J. Vogelzang, MD, FASCO, FACP, Comprehensive Cancer Centers of Nevada
Published: Thursday, Mar 08, 2018



Transcript: 

Daniel George, MD: Hello, and thank you for joining this OncLive® Peer Exchange® titled “Therapeutic Sequencing Strategies for Advanced Kidney Cancer.” Outcomes for patients with advanced renal cell carcinoma have been significantly improved by the availability of molecularly targeted therapies and now immune oncology–based regimens. However, proper selection of appropriate therapy and management of toxicities remain challenging for oncologists, particularly with availability of exciting new therapies and new combinations. Moreover, high-risk localized disease represents an ongoing challenge, with high recurrence rates and poor survival after nephrectomy. In this OncLive® Peer Exchange®, I am joined by a panel of leaders in the field. We’ll be discussing new data from the GU ASCO 2018 meeting and how and when to use available therapies based on new data. I’m Dr. Daniel George, director of GU Oncology at the Duke Cancer Institute in Durham, North Carolina.

Participating today on our panel are Dr. Neeraj Agarwal, director of the Genitourinary Oncology Program in the Oncology Division at the Huntsman Cancer Institute in Salt Lake City, Utah; Dr. Robert Alter, co-division chief and medical oncologist and hematologist in the Division of GU Oncology at the John Theurer Cancer Center at Hackensack University Medical Center in Hackensack, New Jersey; Dr. Bradley McGregor, an instructor in medicine at the Harvard Medical School and a clinical director of the Lank Center of Genitourinary Oncology at the Dana-Farber Cancer Institute in Boston, Massachusetts; and finally Dr. Nicholas Vogelzang, vice chair of the SWOG GU Committee, professor at the University of Nevada Medical School, associate chair of the Genitourinary Committee for US Oncology Research, and medical oncologist at Comprehensive Cancer Centers of Nevada in Las Vegas, Nevada. Thank you so much for joining us. Let’s begin.

Neeraj, can we start with you? Can you outline for us, particularly for patients with localized kidney cancer after nephrectomy, who’s at risk for disease recurrence?

Neeraj Agarwal, MD: I think I’ll mention the patients at the highest risk of recurrence. Those, in my view, are patients who have what we call a C3 disease: a kidney tumor invading a major vein, such as a renal vein, beyond the kidney tissue, or kidney cancer involved in the local regional lymph nodes. I think those are the patients at high risk of recurrence.

Daniel George, MD: That’s roughly what percentage of patients, do you think, with localized kidney cancer?

Neeraj Agarwal, MD: In my estimate, close to one-third of kidney cancer patients.

Daniel George, MD: So, a subset of kidney cancer patients have these high-risk features that we know are at risk for recurrence. Is recurrence risk 50% or 60% over 5 years? What do you think that number is?

Neeraj Agarwal, MD: Yes, I think that’s pretty close.

Daniel George, MD: Bob, there have been a number of adjuvant studies over the last 10 years that have looked at this. Recently, there has been a new approval for sunitinib for treatment of adjuvant renal cell carcinoma with high-risk features. Tell us a little bit about the data that have led to this approval and some of the other studies that are out there reported in this space.

Robert Alter, MD: Thanks Dan. There was the S-TRAC clinical trial that looked at patients with locally regional clear cell renal cell carcinoma. We’ve got 615 patients in a 1:1 randomization receiving sunitinib at 50 mg daily for 28 days on, 14 days off—or the 4-2 regimen—compared with placebo. Patients took this for 1 year, and the medications were continued until intolerability, patient withdrawal, or disease progression. The data presented around ESMO in 2016 have been published in the New England Journal of Medicine and discussed that there was actually an improvement in the disease-free survival in patients who received certain numbers: a 59% 5-year disease-free survival compared with 51% of patients who had placebo. Actually, the overall survival, which was an endpoint as well, was 6.8 years in patients who received sunitinib compared with patients who received placebo, which was 5.6 years. Based upon the 24% reduction in risk of recurrence based upon those data, it received FDA approval.

There were also several other trials that we’ve seen that have been negative trials. There was the recent study that was presented last year, the PROTECT clinical trial, looking at pazopanib compared with placebo. Our patients initially started off taking pazopanib at 800 mg daily, but due to toxicities, the dose was reduced to 600 mg compared with placebo. When you looked at the data, the intent-to-treat patient population at 600 mg seemed to be a negative study. Yet when you look at the first 400 patients who received the 800 mg, they actually had a 31% decrease in risk of reduction or risk of recurrence. So, it was still questionable. But overall, the intent-to-treat data made it a negative study.

Then we go back to the short clinical trial, which Naomi Haas presented several years ago, that compared as a 1:1:1 sorafenib versus sunitinib versus placebo. Based upon tolerability, the doses were reduced for sorafenib as well sunitinib. That, too, was a negative study.

Transcript Edited for Clarity 

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Transcript: 

Daniel George, MD: Hello, and thank you for joining this OncLive® Peer Exchange® titled “Therapeutic Sequencing Strategies for Advanced Kidney Cancer.” Outcomes for patients with advanced renal cell carcinoma have been significantly improved by the availability of molecularly targeted therapies and now immune oncology–based regimens. However, proper selection of appropriate therapy and management of toxicities remain challenging for oncologists, particularly with availability of exciting new therapies and new combinations. Moreover, high-risk localized disease represents an ongoing challenge, with high recurrence rates and poor survival after nephrectomy. In this OncLive® Peer Exchange®, I am joined by a panel of leaders in the field. We’ll be discussing new data from the GU ASCO 2018 meeting and how and when to use available therapies based on new data. I’m Dr. Daniel George, director of GU Oncology at the Duke Cancer Institute in Durham, North Carolina.

Participating today on our panel are Dr. Neeraj Agarwal, director of the Genitourinary Oncology Program in the Oncology Division at the Huntsman Cancer Institute in Salt Lake City, Utah; Dr. Robert Alter, co-division chief and medical oncologist and hematologist in the Division of GU Oncology at the John Theurer Cancer Center at Hackensack University Medical Center in Hackensack, New Jersey; Dr. Bradley McGregor, an instructor in medicine at the Harvard Medical School and a clinical director of the Lank Center of Genitourinary Oncology at the Dana-Farber Cancer Institute in Boston, Massachusetts; and finally Dr. Nicholas Vogelzang, vice chair of the SWOG GU Committee, professor at the University of Nevada Medical School, associate chair of the Genitourinary Committee for US Oncology Research, and medical oncologist at Comprehensive Cancer Centers of Nevada in Las Vegas, Nevada. Thank you so much for joining us. Let’s begin.

Neeraj, can we start with you? Can you outline for us, particularly for patients with localized kidney cancer after nephrectomy, who’s at risk for disease recurrence?

Neeraj Agarwal, MD: I think I’ll mention the patients at the highest risk of recurrence. Those, in my view, are patients who have what we call a C3 disease: a kidney tumor invading a major vein, such as a renal vein, beyond the kidney tissue, or kidney cancer involved in the local regional lymph nodes. I think those are the patients at high risk of recurrence.

Daniel George, MD: That’s roughly what percentage of patients, do you think, with localized kidney cancer?

Neeraj Agarwal, MD: In my estimate, close to one-third of kidney cancer patients.

Daniel George, MD: So, a subset of kidney cancer patients have these high-risk features that we know are at risk for recurrence. Is recurrence risk 50% or 60% over 5 years? What do you think that number is?

Neeraj Agarwal, MD: Yes, I think that’s pretty close.

Daniel George, MD: Bob, there have been a number of adjuvant studies over the last 10 years that have looked at this. Recently, there has been a new approval for sunitinib for treatment of adjuvant renal cell carcinoma with high-risk features. Tell us a little bit about the data that have led to this approval and some of the other studies that are out there reported in this space.

Robert Alter, MD: Thanks Dan. There was the S-TRAC clinical trial that looked at patients with locally regional clear cell renal cell carcinoma. We’ve got 615 patients in a 1:1 randomization receiving sunitinib at 50 mg daily for 28 days on, 14 days off—or the 4-2 regimen—compared with placebo. Patients took this for 1 year, and the medications were continued until intolerability, patient withdrawal, or disease progression. The data presented around ESMO in 2016 have been published in the New England Journal of Medicine and discussed that there was actually an improvement in the disease-free survival in patients who received certain numbers: a 59% 5-year disease-free survival compared with 51% of patients who had placebo. Actually, the overall survival, which was an endpoint as well, was 6.8 years in patients who received sunitinib compared with patients who received placebo, which was 5.6 years. Based upon the 24% reduction in risk of recurrence based upon those data, it received FDA approval.

There were also several other trials that we’ve seen that have been negative trials. There was the recent study that was presented last year, the PROTECT clinical trial, looking at pazopanib compared with placebo. Our patients initially started off taking pazopanib at 800 mg daily, but due to toxicities, the dose was reduced to 600 mg compared with placebo. When you looked at the data, the intent-to-treat patient population at 600 mg seemed to be a negative study. Yet when you look at the first 400 patients who received the 800 mg, they actually had a 31% decrease in risk of reduction or risk of recurrence. So, it was still questionable. But overall, the intent-to-treat data made it a negative study.

Then we go back to the short clinical trial, which Naomi Haas presented several years ago, that compared as a 1:1:1 sorafenib versus sunitinib versus placebo. Based upon tolerability, the doses were reduced for sorafenib as well sunitinib. That, too, was a negative study.

Transcript Edited for Clarity 
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