Patient Profile 2: A 59-Year-Old Woman with Advanced Renal Cell Carcinoma
A panel of experts in renal cell carcinoma present the case of a 59-year-old woman with renal cell carcinoma and discuss systemic therapy options.
Transcript:
Elizabeth Wulff-Burchfield, MD: We can move on to case 2, which as much as we had such wisdom to share about favorable risk, I feel like I almost never see favorable risk anymore. Talking about intermediate and poor risk will be another opportunity for all of us to learn from one another. With this case, would one of you be comfortable describing it to us?
Rana McKay, MD: I’m more than happy to dive in. This is a 59-year-old African American female previously diagnosed with a left renal mass. She underwent a left radical nephrectomy, showing clear cell RCC [renal cell carcinoma]. She had a T3a N0 Mx tumor that was grade 3, and 9 months later she developed metastatic disease. She has metastases in her liver and retroperitoneal lymph nodes, and has radiographic evidence of disease spread. She has a good performance status, KPS [Karnofsky performance status score] is 90%, hemoglobin is a bit low [at] 11.1 g/dL, but her calcium, neutrophils, platelets are all within normal limits.
Elizabeth Wulff-Burchfield, MD: Thank you so much. In thinking about this individual, Dr Barata,…from what you’re seeing and hearing, does that sound like someone for whom you’d go ahead and start systemic therapy or recommend it being started?
Pedro Barata, MD: Great question. I probably [would,] yes. [With] intermediate risk and anemia less than a year, I would strongly consider it. I would definitely have a conversation with the patient about starting an IO [immunotherapy]-based approach in this situation. If you go back to the case, the fact that the patient developed liver metastases within 9 months of surgery, assuming presurgery scans were negative, that’s not good. That tells you that the disease is moving, and it’s moving quite fast. I’m not sure if the patient is symptomatic or not. It doesn’t sound like she has sarcomatoid or rhabdoid features, so I think it would be very appropriate to consider nivolumab and ipilimumab. I think also it would be very appropriate to consider axitinib-pembrolizumab, cabozantinib-nivolumab, or lenvatinib-pembrolizumab. Those are some of my options. To answer your question, that’s probably what I would do.
Elizabeth Wulff-Burchfield, MD: Thank you. I certainly want to delve into that further because I think all of our practices can look somewhat different despite being guideline concordant. I think this table is such an example of that because we have such really high-quality data showing how these IO-TKI [tyrosine kinase inhibitor] combinations and even single-agent TKI of cabozantinib compare to our prior standard of sunitinib. We are practicing in such a great era to know that our patients can expect much improved outcomes compared to when I was in training. It does mean though that every patient can be such a clinical conundrum because we have so many good options.
When you’re thinking about a frontline regimen to use, [in] our case this woman was intermediate by criteria, but had not only nodal but also liver metastases as her first sites of metastatic progression. Dr McGregor, of course it’s obvious you would use shared decision-making, but if she said, “Doctor, I’ll do whatever you say,” what might you recommend for this individual?
Bradley McGregor, MD: I tend to have the same approach as Rana. I’d do the same thing. Are we playing the long game or the short game? I think with the TKI-IOs, we hit a lot of doubles, maybe even triples, but are we hitting that grand slam? We hope for that with nivolumab-ipilimumab.
In this situation, even though there are liver metastases, if the LFTs [liver function test results] are fine and asymptomatic, I still feel comfortable with nivolumab-ipilimumab. I’ve seen responses in patients with liver metastases that can be quite dramatic pretty early, so I do feel comfortable with nivolumab-ipilimumab in a situation like this. Again, not only for the potential for that durable response but for that durable treatment-free interval. As we look forward to more long-term follow-up with TKI IOs, we hope to have maybe 5 years of follow-up with these, that’s great. But if you’re on a TKI for 5 or 6 years, as you alluded to, that has a lot of impact on their quality of life and where [a patient is]. The idea that maybe you give 2 years of immunotherapy and then they will be off of it is very appealing. I agree.
If a patient has a large burden of liver metastases, or symptomatic disease, I’m going to go with the IO-TKI because the chance of PD [progressive disease] with cabozantinib-nivolumab and lenvatinib-pembrolizumab is 5% to 6%. Your chance of disease going through that is incredibly low. If I think they can be in that 1 of 5, even though they progress, and I can salvage with a TKI in the second line, I’m going to go with nivolumab-ipilimumab.
Elizabeth Wulff-Burchfield, MD: If this patient was highly symptomatic and you were concerned about how likely it was for her to be salvageable after nivolumab-ipilimumab, do you have a particular TKI-IO regimen that you might prefer?
Bradley McGregor, MD: I think ultimately they’re all great. I’ve used them all on and off trial. The important thing is if you’re doing this all the time, we can have these nuanced discussions about this vs that. I think if you’re doing this rarely and see on average less than 5 patients with kidney cancer a year, [then] finding the IO-TKI regimen you’re comfortable with and getting familiar with the dosing and understanding that is going to be really important as you pick the right regimen.
Elizabeth Wulff-Burchfield, MD: Great. Thank you, I really appreciate that. Dr Barata, it sounded like you were alluding to your hope that this person might be able to receive nivolumab-ipilimumab, but if she was highly symptomatic, as you said, you might choose a different regimen. Would you have a particular favorite in a case like this?
Pedro Barata, MD: I don’t think favorite is the right word to use, at least in my practice. To be honest, the trials we have in the front line or upon progression do impact how I decide things. For instance, we had a study where we enrolled for the role of debulked nephrectomy. At that time they allowed us to do axitinib-pembrolizumab. We felt comfortable with that approach, but now cabozantinib-nivolumab and lenvatinib-pembrolizumab are available, so we tend to use those.
If you have a second-line study studying cabozantinib with something else, such as cabozantinib-belzutifan vs lenvatinib for example, perhaps that will impact a bit how you decide in the front line. We are biased because the studies we have available at a given time at our sites can impact [the decision as well], understanding that the thought process is an IO-based combination is the way to go.
Overall, cabozantinib-nivolumab is one of my preferred options because of the safety profile combined with the durable efficacy results I’ve seen, when I’m not considering nivolumab-ipilimumab. With that said, I have definitely done lenvatinib-pembrolizumab when I’m looking for a really high response rate in that particular patient. And as I said in the past, I was using axitinib-pembrolizumab very comfortably. That I guess would be my answer. I don’t think I have 1 piece of data that would say I'd definitely go hard for any particular IO-TKI.
Elizabeth Wulff-Burchfield, MD: It sounds like a lot of what you all have alluded to is the notion that a lot of the time we’re playing 3-dimensional chess at our academic centers and trying to think about what options we’d like to reserve for our patients, particularly if there are systemic therapies that are the backbone of potential subsequent-line trials. It also sounds to me like the conclusion is that there aren’t any particular data that would make anyone shy away from any of these regimens. There’s nothing that makes any completely [wrong].
Among these TKI-IO regimens and nivolumab-ipilimumab, it sounds like if someone is not symptomatic, then [there are] none we would clearly rule out. If they are symptomatic, [there is] nothing we would clearly rule in. However, it sounds like there is a trend toward potentially using lenvatinib-pembrolizumab for patients who need debulking due to that overall response rate data, perhaps. I also love the insight and the point about, this individual had her nephrectomy up front when she appeared to have curative-intent disease, but if we’re reserving that, the half-life of these agents could be a really important factor.
Transcript edited for clarity.
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