Eric Jonasch, MD
Between the frontline and second-line settings, there are multiple treatment options available for patients with renal cell carcinoma (RCC), but it is critically important for oncologists to decide on an agent with a patient’s characteristics—and goals—in mind, according to Eric Jonasch, MD.
“That gives you an idea of which agent to give to them and, when they’re on the agent, you’re making sure that you maintain channels of communication so you can listen to what the side-effect profile is that they’re developing,” said Jonasch, who chaired the 2017 OncLive®
State of the Science Summit on Genitourinary Cancers. “You can react in a way that the patient can have maximum quality of life; that is critical. It is probably true for all oncology treatments, but it’s especially true for these targeted agents.”
While the second-line setting had a recent emergence of FDA-approved agents with cabozantinib (Cabometyx), nivolumab (Opdivo), and the combination of lenvatinib (Lenvima) and everolimus (Afinitor), researchers are also discussing the frontline potential of cabozantinib, based on results from the phase II CABOSUN study.
In the trial, cabozantinib reduced the risk of progression or death by 34% versus sunitinib (Sutent) as frontline treatment for patients with metastatic RCC. Additionally, the median progression-free survival (PFS) was 2.6 months higher with cabozantinib versus sunitinib, and the overall response rate (ORR) was 46% versus 18%, respectively. However, longer follow-up is needed, said Jonasch.
In an interview during the meeting, Jonasch, professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, spoke on the evolving choices for patients with RCC in these settings, as well as the remaining challenges in the field.
OncLive: Can you provide an overview of your presentation on RCC?
: The presentation tonight really was to summarize first- and second-line treatment for RCC in 2017. We have had a lot of approvals in the last couple of years, and these obviously make the decisions for which agents to use and what sequence a little bit more interesting.
We have, for example, recent data on cabozantinib in the frontline setting, which has not yet been approved. I want to talk a little bit about why it is that we don’t think it’s quite ready for primetime—although it may be with further analysis.
I’m also going to talk in the second-line setting about the richness of choices we have with agents like nivolumab, cabozantinib, and also lenvatinib and everolimus. Those various agents obviously have distinct properties, side effects, and may also be valuable for one patient more than the other, depending on what their comorbidities are. It’s certainly very interesting; it is an exciting time for RCC. I hope this is going to be helpful for people.
You made a couple of statements about frontline cabozantinib. What is the rationale that this agent might not yet be ready for this setting?
The CABOSUN study randomized a bit more than 150 patients between sunitinib and cabozantinib. These individuals had intermediate- and poor-risk features. The PFS for cabozantinib was clearly superior to that of sunitinib, but there were a couple of things about the trial.
First, it did not have independent review. Second, a number of individuals who were on sunitinib came off very early in the study, which may have skewed the curves somewhat in favor of cabozantinib. We are awaiting independent review of these data and, if they do really show that cabozantinib is superior to sunitinib, it’s going to be an agent that we can think about in individuals who have intermediate- and poor-risk features.
The other thing that cabozantinib seems to be doing is bone in a positive way—in a way that agents like sunitinib and pazopanib (Votrient) don’t. If we do get approval in the frontline setting for cabozantinib, it will give us options for individuals who have bone-predominant metastatic disease, or also high burden of disease where you really need to get tumor reduction in a rapid fashion.
Do you foresee there being potential combination treatments with cabozantinib?
A number of companies are trying to combine cabozantinib with checkpoint antibodies. So far, these data suggest that it is combinable and we need to see whether or not this actually turns into a viable option from an efficacy perspective.