Goals of Therapy in Advanced RCC

Transcript:Robert A. Figlin, MD: That helps us understand the next set of questions that we have with our patients.

David F. McDermott, MD: Right.

Robert A. Figlin, MD: And, Tom, what do you talk to your patients about about goals of therapy, how you’ve chosen their characteristics? You know, we’re always talking about personalized treatment for cancer these days. So, what’s that conversation like, and how do you think about it?

Thomas Hutson, DO, PharmD: I think it’s probably the most important discussion that we, as medical oncologists, have with our patients, and that usually it occurs during that first consultation. Oftentimes, as a medical oncologist—at least in my practice, I’m sure it’s represented in everyone here—we’re the first ones that actually have emotional-filled conversations with patients where we’re actually talking about their mortality. So, in that conversation is natural goals of therapy and laying out to the patient that metastatic kidney cancer—although we’ve made a lot of advances over the past several years, and many of these advances they may be aware of because they’re in the news and in the press—that it’s still not a curable cancer.

But despite that, we have new therapies that can allow them to have a meaningful extension in their life with, hopefully, maintaining quality of life. I’m stressing with them that these are the goals that we can accomplish with the current plethora of drugs that we have available to us. And then allowing the patient to respond to me with what their goals of therapy are. This is where you get that individualized approach. It may be a patient you see that has children—they want to get to graduation or they have a marriage—and you can start tailoring your choice of therapies superficially with that discussion.

Then, the next step going down is actually more to the science and what the clinical trials tell us. Are there patient populations from the group of drugs that seem to benefit with one therapy over another? Is there a particular disease, or comorbidities, that would lend itself to choosing one agent over the others? And we’re all sophisticated enough at this table—and I think many of our medical oncology colleagues out there are too—where we’re able to dissect the data out. And we know that certain classes of drugs that we have—the VEGF inhibitor class, for instance—are going to have their set of toxicities; for instance, cardiovascular toxicities. Therefore, if we have a patient that has comorbidities that are along that line, it may give us pause and have us choose one or the other.

Another class, for instance, would be mTOR inhibitors, which have their own unique toxicities; for instance, diabetes issues and things for the patients with viral diabetes. So, I think there are ways with the drugs that we have to individualize the choice of therapy based upon patient characteristics. The tumor characteristics we alluded to already—the pace, the rapidity, and how fast the cancer’s growing—may allow you to choose one agent or another. But as we all know, we have a standard kind of protocol that we follow, a paradigm. A lot of us will use NCCN guidelines, etc, that list out agents. There have been drugs that have been approved in particular settings. If we’re starting off with initial therapy and we make the decision we’re not going to wait in this patient, I think that’s important to consider. But if we need to start systemic therapy, then we know that we’ve got clinical trial options for our patients. And then we’ve got commercially available drugs—generally, right now, most of us would think of two drugs, they’re both VEGF inhibitors, Sutent and Votrient—as being options to choose from, and that’s how I’d go.

Robert A. Figlin, MD: So, David, most of us are old enough to remember when most of the endpoints for clinical trials were PFS and response rates. And we’re entering an era where we now have approved drugs—cabozantinib, nivolumab—where there’s clear and pivotal evidence to demonstrate survival enhancement. How do you think that fits into the discussion of goals of therapy, currently, as compared to where we were a decade ago when it was not as robust a dataset?

David F. McDermott, MD: Well, I think it’s exciting to be able to tell patients—in some cases, for the first time—that we have drugs that improve overall survival. That’s an endpoint that means something even to the layperson. These drugs are going to help you live longer. Explaining progression-free survival to the average patient is not an easy discussion to have. So, to be able to say—for the first time—that we have not just one but we have two drugs that can lengthen your life in a meaningful way is great. I think being able with further follow up from both studies, we may be able to give them a sense of how likely they are to be alive at certain points—2 years, 3 years, 4 years. For both studies, we don’t have that information yet, but it’s a sign of the impact of some of these treatments.

The improvements in overall survival, both with cabozantinib and nivolumab, are not just statistically significant, they are clinically meaningful. Patients are living much longer. And, for example, in the nivolumab phase III trial, the overall survival for the patients getting nivolumab, the median was 25 months. That is as good in the second-line as we were seeing in the frontline. And that’s not just an nivolumab story, but that’s a story about all the subsequent drugs that are active. Our patients are living, I think, two or three times longer than they were 5 or 10 years ago, and they’re coming back to clinic. And it’s a much different environment to treat patients with kidney cancer these days. You actually have to consider long-term issues, where that wasn’t the case 5 or 10 years ago.

Robert A. Figlin, MD: And I think that really does raise the topic that Tom spoke to, which is that even though some of those results are in the second-line setting, they do impact our conversations with our newly diagnosed patient.

Transcript Edited for Clarity