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Third-Line Therapy and Beyond in Treating Metastatic RCC

Panelists: Daniel J. George, MD, Duke Cancer Center; Robert S. Alter, MD, Hackensack University Medical Center; Chung-Han Lee, MD, PhD, Memorial Sloan Kettering Center; Nizar M. Tamir, MD, FACP, The University of Texas MD Anderson Cancer Center
Published: Friday, Sep 06, 2019



Transcript:

Daniel J. George, MD:
The last area we want to touch on is third-line and beyond. At some point, we just stop counting the line. It’s just sequential therapy. How do you manage some of our localized therapies in this, whether these would be debulking metastasectomies, SBRT [stereotactic body radiation therapy], other palliative radiation forms, using some of those localized therapies to try to debulk the cancer, take down this disease? As we go into multiple lines of therapy, we tend to get fewer objective responses. We’re dealing more with stable disease, and is there an opportunity just to sort of weave in some of these approaches? I’m not giving you a specific example, but I think we’ve all done that. How do you manage that in a multidisciplinary way? Do you work with a tumor board? Do you all bring in radiation oncologists or surgeons to kind of review things? How are you doing it in your academic settings? And then maybe Bob, maybe you can talk a little bit how it is in Hackensack [University Medical Center, Hackensack, New Jersey].

Robert S. Alter, MD: In the community we do exactly what they do in the academic centers. Obviously, it’s multidisciplinary from the minute the patient walks into your office. The urologist is giving you the patient for the most part, and you have to find out again if they’re coming in symptomatic and where’s the symptom from. If they’re having extreme bone metastases in 1 focal region or a brain metastasis  needs to be addressed first. Your patient’s functional quality of life can significantly improve by addressing their symptoms, maybe you sort of take your time. You can actually rethink the situation. You don’t have to feel as if you have to utilize the most aggressive agent which we still don’t know what that is, but we are getting a sense that adding a TKI [tyrosine kinase inhibitor] early to an IO [immune-oncology] may improve that. But still, IO/IO has proven to be just as beneficial.

You remove that symptom and now I say that not just as the first time they walk in your office, but as they progress as well. So let’s say they are receiving second- or third-line and they develop that bone lesion that is symptomatic or epidural extension of a tumor, again 1 that you have to address that. This is really where we have to think about how SBRT can salvage a lot of our patients and we can reposition ourselves on how we can take care of the patients. You hear the IMDC [International Metastatic Renal Cell Carcinoma Database Consortium]—they talk about how less than 40% of patients receive more than 2 lines of therapy—in the clinics and I’m sure in academics as well, we’re seeing these patients being treated with third, fourth, fifth, even sixth lines of therapy, and we are talking about reintroducing fourth-line TKIs on these patients.

I think that when we talk about the care of these patients, we’re not thinking third-line therapy. Again, I like to think about these patients, sequencing them when they come into the office is where I think the CR [complete response] rate from the IO/IO therapy, upfront therapy may actually lead the patients to a durable response later on that you can actually have your patients progress calmly. But, as you mentioned, I think intervening with these patients with multidisciplinary is of utmost importance. At times we have patients that we are treating patients with upfront TKI therapy or maybe soon TKI/IO therapy prior to even considering nephrectomy. And there was an abstract that’s going to be presented that talks about treating these patients with a nephrectomy after receiving their primary therapy. And their overall survival is significantly improved, having these patients undergo nephrectomy after primary therapy as compared to not going to nephrectomy. Even though we receive the patients from urologists, we’re never quite cutting off that door.

Daniel J. George, MD: That’s right.

Chung-Han Lee, MD, PhD: I think that especially for people with symptomatic disease like these local therapies—whether or not it’s SBRT, whether or not it’s ablation—for interventional radiology, these are kind of critical tools that we have or core compression from the neurosurgeon side. Even though we have all these systemic therapies, our confidence about whether or not we’re actually going to get shrinkage or relief of symptoms from these things are probably not as high as like if they had radiation or some sort of local therapy to that lesion.

Nizar M. Tannir, MD, FACP: RCC [renal cell carcinoma] has become a chronic disease. I think we have to integrate and incorporate these palliative or supportive measures with radiation, with cryoablation, or radiofrequency ablation. Our interventional radiologists at The University of Texas MD Anderson Cancer Center in Houston, Texas do a lot of orthopedic intervention for patients who have, say iliac bone metastasis or acetabular hip metastasis, where if the patient is too sick to have surgery, they do a lot of orthopedic intervention to try to palliate the pain and embolization if their renal function is good and they can get a contrast. So I think it’s important to really manage the pain, manage quality of life, improve quality of life. That’s important.

Robert S. Alter, MD: And let’s not forget, if our patients present with hematuria, we still address that. It still may be nephrectomy despite the fact that patient’s tumor burden may be so vast, we’d be thinking about not utilizing nephrectomy, but that may be an important intervention early.

Nizar M. Tannir, MD, FACP: Sure.

Daniel J. George, MD: Go ahead.

Chung-Han Lee, MD, PhD: I was just saying it is a very close collaboration with our colleagues because what we provide is really the context in which how aggressive can they be about the surgery or in the context of the overall prognosis and what treatment options this patient may have down the line.

Daniel J. George, MD: That’s right, what else you have to offer.

Chung-Han Lee, MD, PhD: Yeah.

Daniel J. George, MD: I think these are great insights.


Transcript Edited for Clarity 

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Transcript:

Daniel J. George, MD:
The last area we want to touch on is third-line and beyond. At some point, we just stop counting the line. It’s just sequential therapy. How do you manage some of our localized therapies in this, whether these would be debulking metastasectomies, SBRT [stereotactic body radiation therapy], other palliative radiation forms, using some of those localized therapies to try to debulk the cancer, take down this disease? As we go into multiple lines of therapy, we tend to get fewer objective responses. We’re dealing more with stable disease, and is there an opportunity just to sort of weave in some of these approaches? I’m not giving you a specific example, but I think we’ve all done that. How do you manage that in a multidisciplinary way? Do you work with a tumor board? Do you all bring in radiation oncologists or surgeons to kind of review things? How are you doing it in your academic settings? And then maybe Bob, maybe you can talk a little bit how it is in Hackensack [University Medical Center, Hackensack, New Jersey].

Robert S. Alter, MD: In the community we do exactly what they do in the academic centers. Obviously, it’s multidisciplinary from the minute the patient walks into your office. The urologist is giving you the patient for the most part, and you have to find out again if they’re coming in symptomatic and where’s the symptom from. If they’re having extreme bone metastases in 1 focal region or a brain metastasis  needs to be addressed first. Your patient’s functional quality of life can significantly improve by addressing their symptoms, maybe you sort of take your time. You can actually rethink the situation. You don’t have to feel as if you have to utilize the most aggressive agent which we still don’t know what that is, but we are getting a sense that adding a TKI [tyrosine kinase inhibitor] early to an IO [immune-oncology] may improve that. But still, IO/IO has proven to be just as beneficial.

You remove that symptom and now I say that not just as the first time they walk in your office, but as they progress as well. So let’s say they are receiving second- or third-line and they develop that bone lesion that is symptomatic or epidural extension of a tumor, again 1 that you have to address that. This is really where we have to think about how SBRT can salvage a lot of our patients and we can reposition ourselves on how we can take care of the patients. You hear the IMDC [International Metastatic Renal Cell Carcinoma Database Consortium]—they talk about how less than 40% of patients receive more than 2 lines of therapy—in the clinics and I’m sure in academics as well, we’re seeing these patients being treated with third, fourth, fifth, even sixth lines of therapy, and we are talking about reintroducing fourth-line TKIs on these patients.

I think that when we talk about the care of these patients, we’re not thinking third-line therapy. Again, I like to think about these patients, sequencing them when they come into the office is where I think the CR [complete response] rate from the IO/IO therapy, upfront therapy may actually lead the patients to a durable response later on that you can actually have your patients progress calmly. But, as you mentioned, I think intervening with these patients with multidisciplinary is of utmost importance. At times we have patients that we are treating patients with upfront TKI therapy or maybe soon TKI/IO therapy prior to even considering nephrectomy. And there was an abstract that’s going to be presented that talks about treating these patients with a nephrectomy after receiving their primary therapy. And their overall survival is significantly improved, having these patients undergo nephrectomy after primary therapy as compared to not going to nephrectomy. Even though we receive the patients from urologists, we’re never quite cutting off that door.

Daniel J. George, MD: That’s right.

Chung-Han Lee, MD, PhD: I think that especially for people with symptomatic disease like these local therapies—whether or not it’s SBRT, whether or not it’s ablation—for interventional radiology, these are kind of critical tools that we have or core compression from the neurosurgeon side. Even though we have all these systemic therapies, our confidence about whether or not we’re actually going to get shrinkage or relief of symptoms from these things are probably not as high as like if they had radiation or some sort of local therapy to that lesion.

Nizar M. Tannir, MD, FACP: RCC [renal cell carcinoma] has become a chronic disease. I think we have to integrate and incorporate these palliative or supportive measures with radiation, with cryoablation, or radiofrequency ablation. Our interventional radiologists at The University of Texas MD Anderson Cancer Center in Houston, Texas do a lot of orthopedic intervention for patients who have, say iliac bone metastasis or acetabular hip metastasis, where if the patient is too sick to have surgery, they do a lot of orthopedic intervention to try to palliate the pain and embolization if their renal function is good and they can get a contrast. So I think it’s important to really manage the pain, manage quality of life, improve quality of life. That’s important.

Robert S. Alter, MD: And let’s not forget, if our patients present with hematuria, we still address that. It still may be nephrectomy despite the fact that patient’s tumor burden may be so vast, we’d be thinking about not utilizing nephrectomy, but that may be an important intervention early.

Nizar M. Tannir, MD, FACP: Sure.

Daniel J. George, MD: Go ahead.

Chung-Han Lee, MD, PhD: I was just saying it is a very close collaboration with our colleagues because what we provide is really the context in which how aggressive can they be about the surgery or in the context of the overall prognosis and what treatment options this patient may have down the line.

Daniel J. George, MD: That’s right, what else you have to offer.

Chung-Han Lee, MD, PhD: Yeah.

Daniel J. George, MD: I think these are great insights.


Transcript Edited for Clarity 
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