Treatment Beyond Progression for Metastatic RCC

Transcript:Robert A. Figlin, MD: You’ve chosen an agent for the second-line setting. You’re following their scans and, obviously, their clinical status and their comorbidities. On clinical trials, we use RECIST progression to take them off of this treatment. We have this phenomenon called “pseudoprogression” that’s reported, at least to a certain extent, in the melanoma literature about how I-Os work in cancer. What’s your decision making about stopping therapy, continuing through progression, and not moving on to the next line of therapy until sufficient proof that the current line of therapy is not benefitting the patient?

Eric Jonasch, MD: Bob, let’s speak specifically about nivolumab. What I do is I will re-image every 8 weeks, which is a little different. Some people re-image every 12 weeks, but I’m doing this, in part, because I want to see whether or not there’s pseudoprogression so that we actually have information. I won’t act on progression on nivolumab after 8 weeks unless the patient is dramatically symptomatically deteriorating. And, actually, it’s really interesting to see individuals on nivolumab where you get radiographic progression, but then you see normalization of laboratory parameters. Their anemia goes away, their mild liver dysfunction goes away, they feel better, and their albumen increases. Their body is improving overall, and then you repeat images 8 weeks later and you may start seeing shrinkage in those people. I’ll give a person who has progression, and who feels relatively well on nivolumab, another set of scans 8 weeks later. And if they’re progressed in that second set of scans, I’ll move them on to a different agent.

Robert A. Figlin, MD: Let me just interrupt for a second. Would you say that with the I-Os, you have a more likelihood of defaulting to watching a bit before switching than you might have with a targeted agent?

Eric Jonasch, MD: That was my temptation, and that’s what I started doing. There were presentations at ASCO last year about treatment beyond progression. Now I’ve had some experience, these are anecdotes, but oncologists sometimes live by these, where I’ve been lulled into a sense of security with agents on these I-O agents. Then all of a sudden 6 months later, we have sudden progression in an idiosyncratic manner. So, I’m a little less comfortable just keeping a person on an I-O agent with mild, slow progression because I’ve seen these idiosyncratic changes either in bone or in brain. I will actually move people on to another agent after 6 months for sure if I see this inexorable progression systemically. Again, this is not something that has been validated with level 1 data, but it’s what I feel comfortable with.

Robert A. Figlin, MD: Michael, this is practical stuff. One of the nice things is, as I travel around the country, I’m impressed by how often people watch what we say. We see, in our clinic, a lot of kidney cancer patients every week. Doctors in the community don’t. And what they tend to do, which I’m surprised at, is if I have a patient that I’m planning to see this week with kidney cancer, I’ll go on to OncLive. I’ll see what the group says about how I should be thinking about it, and then I’ll modify my approach based upon the information in the literature that I read. Help the community doctor who’s faced with the infrequent kidney cancer patient to know how to structure their thinking around decision making.

Michael R. Harrison, MD: I think this is a real confusion that I’m seeing from some of my referrals. Before these drugs, nivolumab and cabozantinib, were approved, I was primarily seeing mainly first-line patients and the very refractory patients. But now I’m getting calls and getting these patients referred essentially at second-line. And what should we do? Should we do nivolumab? Should we do cabozantinib? And sometimes also, as Eric said, because of the story of pseudoprogression, maybe after the first scan of nivolumab, what do we do? I agree with Eric. Before this last ASCO with the story from the FDA and Dr. Escudier’s group about pseudoprogression, I was probably lulled into a false sense of complacency just saying on whatever the first scan is, I’m going to give them a little more time. I’m not doing that as much because I have been anecdotally burned by being complacent like that. I guess to circle back and give a practical recommendation, in that patient who’s treated in the first-line with a VEGF receptor TKI, treated in the second-line with nivolumab, at their first scan if they do have pretty clear progression, I’m switching them at that point.

Again, anecdotally, one thing that I have seen is what appears to be what I’m referring to as a “tail wind effect.” This is a little provocative, but a tail wind effect meaning that when I give nivolumab, whatever I give next seems to work a little bit better, and I can only speculate why that is. There were data presented at ASCO about patients who had lived 3 years or more, even with the best response of progression on nivolumab, who seemed to have a benefit. There are limitations to that data.

Robert A. Figlin, MD: But I think we’ve all experienced that, and it’s going to be an interesting paradigm when we start to think about how to generate next-generation data in terms of when we think about targeted agents. We’ve kind of lumped them. But maybe prior I-O therapy may set the patient up to be somewhat different.

Transcript Edited for Clarity