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CABOSUN: Upfront Use of Cabozantinib for mRCC

Insights From: Dan J. George, MD, Duke Cancer Institute
Published: Wednesday, Oct 04, 2017



Daniel James George, MD: At ESMO 2017, we saw the updated independent review of the CABOSUN data. And this was important because some people were concerned when this was presented last year from the Alliance Cooperative Group that, perhaps in an uncontrolled radiographic setting of investigator assessments, some of these data might be somehow biased one way or the other. This was not a blinded study and this was done largely in a community setting, and frankly, the results were astonishing. By investigator assessment, we had a 46% objective response rate for cabozantinib in an intermediate- to poor-risk patient population versus about 20% for sunitinib—so a fairly dramatic difference between those 2—as well as about a 3-month difference in progression-free survival. So, I think those results caught some folks by surprise.

In the past when we’ve compared agents to sunitinib, we’ve seen relatively equivalent results, such as with Votrient, or pazopanib. I think people were a little bit surprised by these results. And so, the independent review was much anticipated and I think very reassuring to see that it very much was consistent with what the investigator assessments are. That’s important for 2 reasons: 1) because I think it adds another layer of validity to these data and 2) because I think it also gives us comfort to know that our assessments as clinicians in the field are pretty accurate.

Lastly, toxicity was an issue with both drugs. These are multitargeted inhibitors that carry with them risks, including diarrhea, fatigue, hypertension, and other physical manifestations from the drug. They were fairly balanced in both the incidence of severe toxicities and overall toxicities, and we saw, again, a similar number of patients who were able to tolerate this drug until disease progression. So, overall, I think this suggests that cabozantinib is a very attractive frontline agent for the intermediate- and poor-risk patients whom we might otherwise treat with sunitinib.

Now, the final question might be, how does that fit with the ipilimumab/nivolumab data that suggest that that also is an accurate regimen for this intermediate- and poor-risk patient population? And I don’t know the answer to that. I think that’s going to require further studies, and I think some of those studies should compare those regimens head-to-head. And I think some of those studies ought to look at those regimens both in terms of combinations together or in sequence. So, we’re excited in the field of kidney cancer. I think ESMO 2017 has left us with more to do, but it’s great to know that we have now multiple treatment options for our patient population, particularly the intermediate- and poor-risk population where we really need them.

Transcript Edited for Clarity 
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Daniel James George, MD: At ESMO 2017, we saw the updated independent review of the CABOSUN data. And this was important because some people were concerned when this was presented last year from the Alliance Cooperative Group that, perhaps in an uncontrolled radiographic setting of investigator assessments, some of these data might be somehow biased one way or the other. This was not a blinded study and this was done largely in a community setting, and frankly, the results were astonishing. By investigator assessment, we had a 46% objective response rate for cabozantinib in an intermediate- to poor-risk patient population versus about 20% for sunitinib—so a fairly dramatic difference between those 2—as well as about a 3-month difference in progression-free survival. So, I think those results caught some folks by surprise.

In the past when we’ve compared agents to sunitinib, we’ve seen relatively equivalent results, such as with Votrient, or pazopanib. I think people were a little bit surprised by these results. And so, the independent review was much anticipated and I think very reassuring to see that it very much was consistent with what the investigator assessments are. That’s important for 2 reasons: 1) because I think it adds another layer of validity to these data and 2) because I think it also gives us comfort to know that our assessments as clinicians in the field are pretty accurate.

Lastly, toxicity was an issue with both drugs. These are multitargeted inhibitors that carry with them risks, including diarrhea, fatigue, hypertension, and other physical manifestations from the drug. They were fairly balanced in both the incidence of severe toxicities and overall toxicities, and we saw, again, a similar number of patients who were able to tolerate this drug until disease progression. So, overall, I think this suggests that cabozantinib is a very attractive frontline agent for the intermediate- and poor-risk patients whom we might otherwise treat with sunitinib.

Now, the final question might be, how does that fit with the ipilimumab/nivolumab data that suggest that that also is an accurate regimen for this intermediate- and poor-risk patient population? And I don’t know the answer to that. I think that’s going to require further studies, and I think some of those studies should compare those regimens head-to-head. And I think some of those studies ought to look at those regimens both in terms of combinations together or in sequence. So, we’re excited in the field of kidney cancer. I think ESMO 2017 has left us with more to do, but it’s great to know that we have now multiple treatment options for our patient population, particularly the intermediate- and poor-risk population where we really need them.

Transcript Edited for Clarity 
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