Considering How Favorable Risk Affects Treatment in ccRCC

Daniel J. George, MD (Moderator)

Eleanor Easley Distinguished Professor in the School of Medicine

Professor of Medicine, Medicine

Professor in Surgery

Duke Cancer Center

Durham, NC

CASE SUMMARY

• A 61-year-old man, married, father of 2 grown children and 5 grandchildren who live nearby, active lifestyle (daily walks, golfs regularly)​
• History of low-volume, indolent metastatic clear cell renal cell carcinoma (ccRCC), status post‒left nephrectomy and adrenalectomy​
  • Based on low-volume, indolent disease, and patient preference – observation only​
• At 1.5 years post-nephrectomy CT scan: ​
  • New paratracheal lymph node (2.0 x 1.5 cm) and more than 10 pulmonary nodules on CT​ scan
  • Lung biopsy confirmed metastatic ccRCC​.
  • Laboratory results: within normal limits​
  • ECOG performance status: 0

DISCUSSION QUESTION

• Approximately what proportion of your patients with metastatic RCC are like this one with favorable risk?

Daniel J. George, MD: How often do you see cases like this? Is this the [usual type of patient] coming into your referral base, or are they more [severe] type cases? What’s typical for you in your practice?

Rajesh Bajaj, MD: I would say about 25% of patients are like this; 75% are more aggressive.

George: I think that's fair. It's nice to see that in the community. In registries we've done, it's been somewhat less than that and I do worry if things are changing. It seems to me like I see more aggressive cases. Maybe that’s because [oncologists] are so good at managing these patients with favorable risk in the community setting, they don't come to us anymore.

Mohamed K. Mohamed, MD: I see more of these type of cases. I run the thoracic program at Cone Health Cancer Center, so most of these present as lung nodule and mediastinal lymphadenopathy. Initially, it could be lung cancer, and they tend to have metastatic renal cell carcinoma. These are the ones that I keep most of the time because I was the only medical oncologist there, so I try to handle it as much as I can.

George: That’s a great point. What happens is those with favorable risk stay with you for years and years, and you can forget about the intermediate- and poor-risk patients, because you get so many patients. But these patients keep coming back so you start thinking you have a lot of them.… you remember them because they're memorable cases. I don't keep strict statistics on this, but I think you're right. There are a lot of these cases that you're not actively managing; they have scans every 6 months or so, but they're out there.

POLLING QUESTION

DISCUSSION QUESTIONS

• To what extent is risk status a deciding factor in your first-line treatment decision making?​
• What drives your selection of first-line therapy for favorable-risk, metastatic ccRCC? ​

Thai H. Ho, MD, PhD: I think quality-of-life data may be different for patients who are taking [immunotherapy (IO) plus tyrosine kinase inhibitor (TKI)] vs when they get nivolumab [Opdivo]/ipilimumab [Yervoy].

George: Some of the issues are how our immunotherapies are working in these sites like the brain or the liver, where we know we can get penetration with TKIs in there. And these are vascular lesions. I think some of that's a factor.

You don't see sarcomatoid much in favorable-risk patients. It tends to be more in intermediate- and poor-risk, but it's possible. There's exceptions to everything, so it's certainly something to consider.

What about quality of life and safety? How do people feel about the quality of life for these patients? These are long-term survivors. Do you feel one way or another about IO/TKIs vs IO/IO combinations?

Govinda R. Brahmanday, MD: I use both [types of] regimens. In general, I feel that the TKI component is definitely harder on patients, especially cabozantinib [Cabometyx] and axitinib [Inlyta] too, with significant fatigue and hand-foot syndrome as issues. If the patients do well with nivolumab/ipilimumab, they usually do not have a problem. If they do have a problem, that could be pretty intense, especially with adrenal insufficiency. I had a patient who ended up having insulin-dependent diabetes, a very rare, but definitely life-changing event for the patient.

George: I think it’s a good point. Unfortunately, when we get toxicities from nivolumab/ipilimumab, they tend to be durable as well. Some of them are permanent, and others can last weeks. We can run into real trouble. If you treat enough patients, you’re going to have some die from it; I have. You learn and know what to look for as early signs. You definitely have to be careful. And it's not always early on. Some of these toxicities happen in the third or fourth cycle. So, you're not out of the woods with that. Those are the tricky things. With the TKIs, the adverse events are more common, but they're also more reversible when you hold the TKI. It gives you an out for some of these patients, and that's important.

[There is also] the fast onset with TKIs. I think that's key as well. For our intermediate- and poor-risk patients, safety and quality of life matter. But at the end of the day, this is still—even in the patients with favorable-risk metastatic disease—a lethal disease for the majority of patients looking out 5 to 10 years. It's not like our patients with chronic lymphocytic leukemia or indolent prostate cancer. This is still disease, even in the best of scenarios, that can progress and can be unpredictable. Certainly, these are patients we need to keep close tabs on.