Initial Therapy for Advanced Renal Cell Carcinoma - Episode 5
Elizabeth R. Plimack, MD: The favorable-risk patient often requires the longest conversation in terms of treatment options because truly, they have many treatment options. For many of those patients, observation or surveillance is an option. And as you’re going along the spectrum of less intervention to more intervention, while combination therapies are standard for poor- and intermediate-risk patients, the favorable-risk patient may not need a combination therapy. When it’s time for treatment in that patient population, perhaps a single-agent VEGF inhibitor might be the best way to start.
How do we make these decisions among surveillance, single-agent VEGF inhibition, and combination VEGF-immunotherapy for favorable-risk patients? It’s a conversation with the patient. A lot of it is, how aggressive do they want to be with their cancer? What’s their appetite for potential adverse effects? Immunotherapy adverse effects aren’t always reversible and certainly take longer to reverse, although they’re rarer. Adverse effects from a VEGF TKI [tyrosine kinase inhibitor] are reversible as soon as you hold the drug for the vast majority of cases.
The risk-versus-benefit conversation is different. And for the truly conservative patient or the older patient who has comorbidities or for whom any adverse effect of treatment might have a bigger impact, there’s surveillance or observation. Doing that even for a few scans also allows you to get a sense of the pace of the disease. These are all the things we talk about, often over 2 visits to let things sink in, share data, and give patients options. But many people will elect observation if it’s offered to them initially, and then for patients on observation when I do start treatment, often I will start gently with 1 agent, layering it in combinations later.
VEGF inhibitors are oral; immunotherapy so far is only IV [intravenous]. Those 2 different modalities have some logistical implications for the patient. I find patients are much more interested in the difference in efficacy and adverse effects. But intravenous therapy does require trips to the center periodically, usually every 3 weeks for the agents we use. The oral drugs can allow for more time away from the center, but cost can be an issue because prescription plans vary more than medical plans, which in the United States are what cover intravenous medication. It seems like a major concern for patients, but if their insurance can cover either option, it ends up being a discussion around adverse effects and efficacy. I find patients are willing to use intravenous or oral therapy depending on those other factors.
Eric A. Jonasch, MD: One of the key questions we really need to ask ourselves when we’re treating an individual with newly diagnosed favorable-risk renal cell carcinoma is, do we give them a TKI—I/O [immuno-oncology] combination, like axitinib and pembrolizumab? Or do we give them a TKI monotherapy? We have to look at the results of the trials.
The axitinib-pembrolizumab combination resulted in an objective response rate of 59%, a progression-free survival of close to 16 months, and an overall survival advantage over sunitinib monotherapy. Although these 3 agents are in the preferred category, we will likely rapidly see a change in the way these recommendations are being made. Personally, for an individual with good-risk features, I would probably start them on axitinib plus pembrolizumab.
Elizabeth R. Plimack, MD: One of the things we talk about with the favorable-risk patient when we’re talking about initial therapy is whether we do single-agent VEGF inhibition or combination VEGF inhibition with immunotherapy. So far, the data for survival with VEGF inhibition plus immunotherapy are excellent, but those data are for all comers. When we separate it for favorable-risk patients, the curves don’t separate as much. The combination doesn’t gain as much over the single agent as with poor- and intermediate-risk patients. The conversation I have with patients is that we can start gently. We can start with 1 agent and see how you do and reserve the immunotherapy for next line if it doesn’t work. We all have patients in our clinic who are on their first drug, a VEGF inhibitor alone, for a really long time with good control. And then you know it was the right choice.
We don’t yet know exactly, though, who the patients are who are really going to gain more benefit from a combination versus a single agent. I see it as more philosophical. If you’re taking someone from observation and you’re doing everything slowly and gently, 1 step at a time makes sense. You could start with a VEGF inhibitor by itself. If you’re going strictly by the data and just want the most impactful therapy, right now that’s probably the combination.
Transcript Edited for Clarity