Sumantha K. Pal, MD

This transcript has been edited for clarity.

Hi, I’m Doctor Monty Pal, and I’m a medical oncologist at City of Hope Comprehensive Cancer Center.

I run the kidney cancer program there, and it’s really been amazing to see the tidal wave of new therapies that we’ve developed for kidney cancer over the years.

What I will say is that most of the treatments that we have, the doublet therapies and adjuvant treatments, really pertain to the most dominant subset of kidney cancer, and that’s clear cell; that really represents about 75%-80% of all cases of kidney cancer.

Having said that, I’d like to focus on perhaps a less dominant subset of kidney cancer known as papillary. This represents about 15%-20% of cases.

To be fair, there are other rare subtypes and those certainly warrant focus as well: Chromophobe represents about 5% of all diseases; translocation, unclassified, a percentage point or 2.

But papillary really is a setting in which we can do — and as I’ll demonstrate, have done — clinical trials.

Now papillary kidney cancer is similar in terms of its demographics to clear cell renal cell carcinoma (RCC). There still tends to be a male predominance. It may have a slightly lower age of initial presentation, but otherwise there’s many commonalities.

I do think one of the areas where it differs, and this is critical, is in the context of biology: We think that papillary RCC is really driven by the MET proto-oncogene amongst other things. With that in mind, there have been a whole host of therapies directed at the MET proto-oncogene, and we’ll discuss that in just a moment.

I wanted to first talk about management of localized papillary kidney cancer. This management doesn’t differ significantly from what we would perhaps consider in the context of localized clear cell kidney cancer. For stage 1 through 3 disease, patients still receive surgery as the mainstay, and I would argue that, in the context of stage 4 disease, we should still really consider aggressive local definitive therapies if at all possible.

Having said that, the role of adjuvant therapy is a bit unclear in this context. I would suggest that in the context of adjuvant therapy for papillary kidney cancer, it’s a bit of a no go until we have greater data in this setting. Therapies like pembrolizumab and sunitinib really were only tested in the context of clear cell disease.

And with that background, I wanted to move into metastatic disease. For patients with stage 4 papillary kidney cancer, therapy may or may not resemble the treatments that we use for clear cell kidney cancer.

There have been trials in yesteryear with really creative names, ASPEN and ESPN for instance, that actually juxtaposed older therapies against one another. Sunitinib against everolimus, for instance, was common to both of those studies. And it really suggested perhaps that sunitinib was the preferred choice between those two targeted therapies. Sunitinib then became a bit of a standard when it came to randomized trials, and in fact, it still remains something that’s incorporated as a base regimen at phase 3 clinical trials.

I’ll show you that in the PAPMET clinical trial, which was a randomized phase 2 experience, we were able to compare sunitinib to cabozantinib, crizotinib, and savolitinib. The latter three drugs are all so-called MET inhibitors. And what’s quite interesting about this study is that cabozantinib, the dual VEGF/MET inhibitor, really is the one that seemed to win out.

When you look at median progression-free survival (PFS), in sunitinib in that study was around 6 months. When you look at cabozantinib, it was around 9 months.

Having said that, with cabozantinib, there was no overall survival advantage, and I will say that the PFS benefit is modest. So, we still need more in the way of clinical trials.

To that end, there’s a number of single arm studies supporting cabozantinib-based regimens, cabozantinib/atezolizumab and cabozantinib/nivolumab, with healthy response rates. For papillary kidney cancer, the response rate with those regimens is around 43%-47%.

In the context of lenvatinib and pembrolizumab, we actually see the response rate augmented to approximately 53%.

So, with those numbers in mind, I definitely think that doublet therapy is promising, but as we always tell our fellows in the clinic, randomization is really king.

So, we do have two phase 3 clinical trials, STELLAR-304, which is a study that I’m running, and the second study is known as SAMETA. Both evaluate papillary patients, but in very different ways.

STELLAR-304 includes patients with papillary, translocation, and unclassified kidney cancer and randomizes to sunitinib vs zanzalintinib, a novel TKI, with nivolumab.

In contrast, SAMETA takes the very interesting approach of actually selecting out patients with MET abnormalities and randomizing them to sunitinib vs savolitinib.

There are other approaches. For instance, the SUNNIFORECAST study recently assessed nivolumab and ipilimumab. There are randomized phase 2 studies looking at axitinib and pembrolizumab or perhaps axitinib and, sorry, cabozantinib with atezolizumab.

But I do think these phase 3 studies, SAMETA and STELLAR-304, are the ones that are really poised to change the landscape of therapy for papillary kidney cancer.

Sumanta K. Pal, MD, Professor, Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, California, has disclosed the following relevant financial relationships: Received travel from: CRISPR; Ipsen. A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi, I’m Doctor Monty Pal, and I’m a medical oncologist at City of Hope Comprehensive Cancer Center.

I run the kidney cancer program there, and it’s really been amazing to see the tidal wave of new therapies that we’ve developed for kidney cancer over the years.

What I will say is that most of the treatments that we have, the doublet therapies and adjuvant treatments, really pertain to the most dominant subset of kidney cancer, and that’s clear cell; that really represents about 75%-80% of all cases of kidney cancer.

Having said that, I’d like to focus on perhaps a less dominant subset of kidney cancer known as papillary. This represents about 15%-20% of cases.

To be fair, there are other rare subtypes and those certainly warrant focus as well: Chromophobe represents about 5% of all diseases; translocation, unclassified, a percentage point or 2.

But papillary really is a setting in which we can do — and as I’ll demonstrate, have done — clinical trials.

Now papillary kidney cancer is similar in terms of its demographics to clear cell renal cell carcinoma (RCC). There still tends to be a male predominance. It may have a slightly lower age of initial presentation, but otherwise there’s many commonalities.

I do think one of the areas where it differs, and this is critical, is in the context of biology: We think that papillary RCC is really driven by the MET proto-oncogene amongst other things. With that in mind, there have been a whole host of therapies directed at the MET proto-oncogene, and we’ll discuss that in just a moment.

I wanted to first talk about management of localized papillary kidney cancer. This management doesn’t differ significantly from what we would perhaps consider in the context of localized clear cell kidney cancer. For stage 1 through 3 disease, patients still receive surgery as the mainstay, and I would argue that, in the context of stage 4 disease, we should still really consider aggressive local definitive therapies if at all possible.

Having said that, the role of adjuvant therapy is a bit unclear in this context. I would suggest that in the context of adjuvant therapy for papillary kidney cancer, it’s a bit of a no go until we have greater data in this setting. Therapies like pembrolizumab and sunitinib really were only tested in the context of clear cell disease.

And with that background, I wanted to move into metastatic disease. For patients with stage 4 papillary kidney cancer, therapy may or may not resemble the treatments that we use for clear cell kidney cancer.

There have been trials in yesteryear with really creative names, ASPEN and ESPN for instance, that actually juxtaposed older therapies against one another. Sunitinib against everolimus, for instance, was common to both of those studies. And it really suggested perhaps that sunitinib was the preferred choice between those two targeted therapies. Sunitinib then became a bit of a standard when it came to randomized trials, and in fact, it still remains something that’s incorporated as a base regimen at phase 3 clinical trials.

I’ll show you that in the PAPMET clinical trial, which was a randomized phase 2 experience, we were able to compare sunitinib to cabozantinib, crizotinib, and savolitinib. The latter three drugs are all so-called MET inhibitors. And what’s quite interesting about this study is that cabozantinib, the dual VEGF/MET inhibitor, really is the one that seemed to win out.

When you look at median progression-free survival (PFS), in sunitinib in that study was around 6 months. When you look at cabozantinib, it was around 9 months.

Having said that, with cabozantinib, there was no overall survival advantage, and I will say that the PFS benefit is modest. So, we still need more in the way of clinical trials.

To that end, there’s a number of single arm studies supporting cabozantinib-based regimens, cabozantinib/atezolizumab and cabozantinib/nivolumab, with healthy response rates. For papillary kidney cancer, the response rate with those regimens is around 43%-47%.

In the context of lenvatinib and pembrolizumab, we actually see the response rate augmented to approximately 53%.

So, with those numbers in mind, I definitely think that doublet therapy is promising, but as we always tell our fellows in the clinic, randomization is really king.

So, we do have two phase 3 clinical trials, STELLAR-304, which is a study that I’m running, and the second study is known as SAMETA. Both evaluate papillary patients, but in very different ways.

STELLAR-304 includes patients with papillary, translocation, and unclassified kidney cancer and randomizes to sunitinib vs zanzalintinib, a novel TKI, with nivolumab.

In contrast, SAMETA takes the very interesting approach of actually selecting out patients with MET abnormalities and randomizing them to sunitinib vs savolitinib.

There are other approaches. For instance, the SUNNIFORECAST study recently assessed nivolumab and ipilimumab. There are randomized phase 2 studies looking at axitinib and pembrolizumab or perhaps axitinib and, sorry, cabozantinib with atezolizumab.

But I do think these phase 3 studies, SAMETA and STELLAR-304, are the ones that are really poised to change the landscape of therapy for papillary kidney cancer.

Sumanta K. Pal, MD, Professor, Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, California, has disclosed the following relevant financial relationships: Received travel from: CRISPR; Ipsen. A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi, I’m Doctor Monty Pal, and I’m a medical oncologist at City of Hope Comprehensive Cancer Center.

I run the kidney cancer program there, and it’s really been amazing to see the tidal wave of new therapies that we’ve developed for kidney cancer over the years.

What I will say is that most of the treatments that we have, the doublet therapies and adjuvant treatments, really pertain to the most dominant subset of kidney cancer, and that’s clear cell; that really represents about 75%-80% of all cases of kidney cancer.

Having said that, I’d like to focus on perhaps a less dominant subset of kidney cancer known as papillary. This represents about 15%-20% of cases.

To be fair, there are other rare subtypes and those certainly warrant focus as well: Chromophobe represents about 5% of all diseases; translocation, unclassified, a percentage point or 2.

But papillary really is a setting in which we can do — and as I’ll demonstrate, have done — clinical trials.

Now papillary kidney cancer is similar in terms of its demographics to clear cell renal cell carcinoma (RCC). There still tends to be a male predominance. It may have a slightly lower age of initial presentation, but otherwise there’s many commonalities.

I do think one of the areas where it differs, and this is critical, is in the context of biology: We think that papillary RCC is really driven by the MET proto-oncogene amongst other things. With that in mind, there have been a whole host of therapies directed at the MET proto-oncogene, and we’ll discuss that in just a moment.

I wanted to first talk about management of localized papillary kidney cancer. This management doesn’t differ significantly from what we would perhaps consider in the context of localized clear cell kidney cancer. For stage 1 through 3 disease, patients still receive surgery as the mainstay, and I would argue that, in the context of stage 4 disease, we should still really consider aggressive local definitive therapies if at all possible.

Having said that, the role of adjuvant therapy is a bit unclear in this context. I would suggest that in the context of adjuvant therapy for papillary kidney cancer, it’s a bit of a no go until we have greater data in this setting. Therapies like pembrolizumab and sunitinib really were only tested in the context of clear cell disease.

And with that background, I wanted to move into metastatic disease. For patients with stage 4 papillary kidney cancer, therapy may or may not resemble the treatments that we use for clear cell kidney cancer.

There have been trials in yesteryear with really creative names, ASPEN and ESPN for instance, that actually juxtaposed older therapies against one another. Sunitinib against everolimus, for instance, was common to both of those studies. And it really suggested perhaps that sunitinib was the preferred choice between those two targeted therapies. Sunitinib then became a bit of a standard when it came to randomized trials, and in fact, it still remains something that’s incorporated as a base regimen at phase 3 clinical trials.

I’ll show you that in the PAPMET clinical trial, which was a randomized phase 2 experience, we were able to compare sunitinib to cabozantinib, crizotinib, and savolitinib. The latter three drugs are all so-called MET inhibitors. And what’s quite interesting about this study is that cabozantinib, the dual VEGF/MET inhibitor, really is the one that seemed to win out.

When you look at median progression-free survival (PFS), in sunitinib in that study was around 6 months. When you look at cabozantinib, it was around 9 months.

Having said that, with cabozantinib, there was no overall survival advantage, and I will say that the PFS benefit is modest. So, we still need more in the way of clinical trials.

To that end, there’s a number of single arm studies supporting cabozantinib-based regimens, cabozantinib/atezolizumab and cabozantinib/nivolumab, with healthy response rates. For papillary kidney cancer, the response rate with those regimens is around 43%-47%.

In the context of lenvatinib and pembrolizumab, we actually see the response rate augmented to approximately 53%.

So, with those numbers in mind, I definitely think that doublet therapy is promising, but as we always tell our fellows in the clinic, randomization is really king.

So, we do have two phase 3 clinical trials, STELLAR-304, which is a study that I’m running, and the second study is known as SAMETA. Both evaluate papillary patients, but in very different ways.

STELLAR-304 includes patients with papillary, translocation, and unclassified kidney cancer and randomizes to sunitinib vs zanzalintinib, a novel TKI, with nivolumab.

In contrast, SAMETA takes the very interesting approach of actually selecting out patients with MET abnormalities and randomizing them to sunitinib vs savolitinib.

There are other approaches. For instance, the SUNNIFORECAST study recently assessed nivolumab and ipilimumab. There are randomized phase 2 studies looking at axitinib and pembrolizumab or perhaps axitinib and, sorry, cabozantinib with atezolizumab.

But I do think these phase 3 studies, SAMETA and STELLAR-304, are the ones that are really poised to change the landscape of therapy for papillary kidney cancer.

Sumanta K. Pal, MD, Professor, Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, California, has disclosed the following relevant financial relationships: Received travel from: CRISPR; Ipsen. A version of this article appeared on Medscape.com.