NCCN Recommends Lenvima Plus Keytruda for First-Line Renal Cell Carcinoma: What Patients Should Know

The combination use of Lenvima (lenvatinib) plus Keytruda (pembrolizumab) was added as a Category 1 recommendation by the National Comprehensive Cancer Network (NCCN) for the treatment of front-line renal cell carcinoma (RCC).

While these recommendations are intended for oncologists to manage cancer care, it is key for patients to also understand why this regimen is preferred and, moreover, how it can impact their treatment journey.

To help patients better understand the NCCN’s recommendation, and to assist in their conversations with their oncologists, CURE spoke with Eric Jonasch, MD, professor in the Department of Genitourinary Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, Texas, and vice-chair of the NCCN Guidelines Panel for Kidney Cancer.

CURE: Before we get into the new recommendation, can you explain to our patients what the NCCN recommendations are and why they’re important?

Jonasch: The NCCN guidelines, our national coalition of centers of excellence, are organized by cancer type. We have a panel of specialists, including medical, surgical and radiation oncologists that populate these panels. There's a chair and vice chair for each of these panels. The goal really is to assess the different therapies that are available for a particular cancer, and to then make recommendations about the whether these should be used, what the level of evidence is and the level of enthusiasm for these particular therapies.

For example, if you have a clinical trial that is well designed … which usually means it's a randomized study, meaning that it's a study where you have two groups of individuals, one group who receives the standard of care and the other group will receive some sort of experimental therapy. If that trial is well designed and the results show there's a clear benefit for the experimental therapy, then (that drug will) end up getting a level 1 recommendation. And then there's also the preferred status, where the panel can state their preference for specific regimens.

So, this is just a way of allowing physicians to understand where, based on these expert recommendations, these particular treatments lie in the in the treatment armamentarium.

CURE: Why is it significant that the addition of Lenvima plus Keytruda is now recommended as a preferred regimen for patients with first-line RCC?

Jonasch: That's significant because it shows that, across the various therapies or combinations that are available for renal cell carcinoma, this particular regimen would be one of the first ones we would consider using in a particular disease state. This therapy was tested in the front-line setting, meaning individuals have not received prior therapy for advanced kidney cancer. And it is one of the preferred regimens because the strength of the evidence is such that we would want to see this being prioritized.

CURE: What was this recommendation based on?

Jonasch: So this study looked at over 1,000 individuals who had advanced renal cell carcinoma. It was actually three arms: The standard-of-care arm was Sutent (sunitinib); there was an arm with Lenvima plus Keytruda; and there was an arm with Lenvima plus Afinitor (everolimus).

The primary end point of this study was to look at progression-free survival, or the time it took for patients who are on this study to start having their disease grow again. And then there were a number of secondary end points, which are response to therapy, or how much shrinkage there is/ of the tumors, and also overall survival. This trial basically showed various, very strong results in all of these domains.

The progression-free survival was almost two years (23.9 months), compared to nine months for the standard-of-care arm. The overall survival – where we sort of look at the probability of death at a certain point in time or a median point in time – was clearly in favor of this regimen. And also, the response rate, meaning the percentage of individuals who had shrinkage, was almost doubled with this combination. And so, these are very strong data. And actually, even more impressively, the percentage of individuals who had complete shrinkage of their disease was 16%.

All of these various factors, together, show that this is one of the strongest regimens that's been tested so far in this particular setting, in advanced kidney cancer. And so the NCCN panel felt that these data deserve preferred status.

CURE: What does it mean that this is a category 1 recommendation?

Jonasch: A category 1 designation is driven by concordance amongst NCCN panelist and by the strength of the evidence. First, there is concordance amongst the panel that this regimen is efficacious. Second is that the quality of the data are very high. For example, this trial is randomized, there's a sufficiently large number of individuals in the trial that show that it's a robust study, and there are other studies that have supported these results, to show that it is not just a chance occurrence that this trial was positive. So these are the various things that make an NCCN level 1 designation.

CURE: Is there anything in particular patients should know about this recommendation?

Jonasch: Just that the preferred regimens should be prioritized in the consideration of treatment. Having said that, a skilled oncologist who makes these decisions can prioritize those therapies, even within the preferred category. Or there might be some circumstances that will make a preferred regimen not appropriate for a particular patient.

So, this is obviously a conversation that needs to occur between the patient and the physician. The physician can then explain what the different regimens are in these various categories, explain why one would be chosen over the other and whether there may be other choices that are not preferred, but that might actually be ideal for that particular patient for various reasons.

CURE: What do you think patients with front-line renal cell carcinoma have to look forward to now that we have another preferred option in the regime?

Jonasch: We are seeing that overall survival has increased consistently over the past five years, as more and more of these combination regimens have been approved. So, the chance of having a prolongation of survival has become a reality for many patients. The chance of a complete disappearance of disease is no longer a fantasy, but a reality. There is a small percentage of individuals who are cured in 2021, which is amazing. I would have been afraid to say that five years ago.

But, having said that, we are dealing with regimens that carry a real burden of toxicity, and can have an impact on quality of life. So, maintaining that dialogue between the treating team, the patient and the patient’s family to make sure that we can maximize quality of life while we're improving quantity of life is critical.

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