DR GEORGE: I think there are pros and cons to both VEGF inhibitors, pazopanib and sunitinib. And I tend to have conversations with patients about those pros and cons and choosing them, because I think they are slightly different. With pazopanib, we have a number of dose levels that we can use, from 800 mg down to 400 mg. And we have a therapy that is generally pretty well tolerated across a wide age range of patients. And we have toxicities that are slightly different.

We see more liver LFT changes associated with that drug than some of the other drugs in class, but we see, say, less hand-foot syndrome than we do with some other agents in class. So, it’s a little bit of a “picking your poison” discussion with those patients. With sunitinib, we have an agent that we’re using with an on-off schedule. Historically, that’s been a 4-weeks-on, 2-weeks-off schedule, but more recently we’ve used 2 weeks on, 1 week off in a number of patients and seen a little bit less cumulative toxicity associated with more frequent breaks of the therapy.

I think both agents have really pretty equivalent efficacy in terms of progression-free survival and overall survival. So I’ll generally talk with patients about these side effects and, between what their largest concerns are and what we see as maybe fitting their lifestyle best, we’ll choose one or the other. I don’t feel strongly that there’s 1 drug here that fits all patients. And so I like using both of these drugs, and I use them both frequently in my practice at this point in time. And I think there are advantages to each of them.

But let me say this for both, for the entire class: The biggest challenge I see for patients is losing their functional capacity. I’m not talking about performance status, per se. I’m talking about their conditioning. And I think one of the biggest things we don’t address up front for patients is the fact that they’re likely over time to develop significant fatigue, whichever agent we use.

And this fatigue is not simply a qualitative fatigue. We can see its changes on echocardiogram. You can see changes in muscle strength and density. You can quantify. And we’re beginning to do this, quantify their exercise capacity on these agents. And it absolutely declines, unless we mitigate that with proactive exercise. And even these cancer patients with their complications and everything else can do that. And I think it’s increasingly important for our patients to know just how critical it is that they maintain their functional status. Their biggest declines happen in their first cycle of therapy.

And that’s very different from chemotherapies, where there’s more of a cumulative effect of treatment over time. This seems to hit patients up front very early, so it’s really important counseling for folks up front.

Bladder cancer

Prostate cancer

Renal cell carcinoma

Checkpoint inhibitors