Final Overall Survival Results of the CLEAR Study in Renal Cell Carcinoma With Thomas Hutson, MD

Oncology Data Advisor: Welcome to Oncology Data Advisor. Today, we're here at the ASCO Annual Meeting in Chicago, and I'm joined by Dr. Thomas Hutson. Thanks so much for joining me today.

Thomas Hutson, DO, PharmD: I'm happy to be here.

Oncology Data Advisor: Would you like to introduce yourself and share what your research focuses on?

Dr. Hudson: I am a Professor of Medicine at Texas A&M College of Medicine, and I'm the Director of the Urologic Oncology Cancer Research and Treatment Center with Texas Oncology at Baylor Sammons Cancer Center. Also, I have the privilege of being an Associate Director and Phase 1 Director for the Sarah Cannon Research Institute. I'm presenting on the behalf of my co-investigators the final pre-specified four-year overall survival analysis from the phase 3, international CLEAR study. The CLEAR study was a frontline advanced RCC study comparing three different arms: lenvatinib/pembrolizumab, lenvatinib/everolimus, versus sunitinib. The initial results of this were presented and published subsequently in the New England Journal of Medicine over two years ago and resulted in the regulatory approval of the combination of lenvatinib pembrolizumab around the world, and its rapid uptake into guidelines supporting its use as a preferred option for patients in the frontline setting who have advanced renal cell carcinoma.

Oncology Data Advisor: What were the key findings of the final overall survival analysis you're presenting?

Dr. Hutson: In the final overall survival analysis, we're able to report that the robustness of efficacy that we'd seen and previously reported is maintained throughout an additional 23-months of follow-up, which pushes it over the four-year mark. This is not only in overall survival, where we have a hazard ratio that is 0.79, but also in other efficacy end points such as progression-free survival and objective response rate. We have a 71% partial response rate with a complete response (CR) rate of 18%, and again, this tracks and is as robust as previously reported. Additionally, we're able to report that there are no additional safety signals and no additional toxicity with longer follow-up, and toxicity concerns are handled with appropriate dose interruptions and dose reductions. So, at the end of the day, with additional follow-up, the robustness of the lenvatinib/pembrolizumab data is maintained. This should give comfort both to prescribing physicians as well as to patients that the efficacy that was initially reported is indeed maintained without any additional safety signals.

Oncology Data Advisor: That's amazing. How does lenvatinib plus pembrolizumab fit into the current landscape of treatment for renal cell carcinoma?

Dr. Hutson: For advanced renal cell carcinoma, we have somewhat of an embarrassment of riches where we have multiple frontline regiments, which have shown very similar levels of efficacy and tolerability, allowing the physician and patient to really choose amongst several good options. There are no randomized phase 3 head-to-head studies showing security of one regimen or not. What's most important is that the clinician gets comfortable with the regimen they're choosing and feels comfortable that they're going to get the expected benefits that are seen. The lenvatinib/pembrolizumab regimen is one of the, if not the most powerful regimens that we have to date based upon data alone from this pivotal phase 3 CLEAR study. So, that becomes a major treatment option for physicians to select as a frontline treatment. Again, having more options is always a positive when it comes to allowing the doctor and patient to individualize their treatment and select a regimen that they think will meet their goals of greater efficacy and tolerability.

Oncology Data Advisor: In light of all these options, how do you personally decide which options to use for patients?

Dr. Hudson: Yes, so it's been a joy in my career to be involved intimately in the drug development of most of the regimens that we have in kidney cancer, and so I've been able to use them all in my clinic. I have a large enough population of this cancer to do that. Right now, my new starts are preferentially getting an immune-oncology/tyrosine kinase inhibitor (IO/TKI) regimen, and that regimen preferentially is lenvatinib pembrolizumab. I feel very comfortable with the predictable side effect profile and the efficacy I rely on, and that translates well from the clinical study into the real-world patient sitting in front of me.

Oncology Data Advisor: Great. Are there any trials that are being presented here in RCC or trials that you're looking forward to hearing results of?

Dr. Hutson: Well, there's nothing new as far as a blockbuster new mechanism of action or anything that's pushing the field that much further. What we're seeing at this year's ASCO is a report of CONTACT-03, which is a novel combination of a programmed death ligand 1 (PD-L1) inhibitor with cabozantinib. Again, we expect to see a similar level of activity as we see with the IO/TKIs in general for that, but again, we'll have to wait for that presentation to see the data. And then we do see updated results from axitinib/pembrolizumab (axi/pembro), which is the other IO/TKI that use utilizes pembrolizumab as the IO backbone. Then we see the four-year updated results that I'm presenting on pembro and lenvatinib. And so, what we can say for a class of IO/TKIs is that these agents are robust in their activity, that this activity seems to be maintained no matter which regimen you're choosing throughout the duration of follow-up, and that they're very tolerable. If anything, it solidifies the role of IO/TKI as the standard-of-care regimen that the vast majority of patients should be receiving as initial therapy.

Oncology Data Advisor: Awesome. One last question I'll ask you is, since the theme of ASCO this year is "Partnering with Patients," how do you personally do this in your practice treating patients with RCC?

Dr. Hutson: This theme of "Partnering with Patients" translates well into my practice because that, to be honest with you, is how I've built my practice from day one. It comes back to why I chose to become an oncologist, which is to be the patient advocate, having my own personal family history of cancer and wanting to make it better. The regimens that we choose in kidney cancer allow me to do that again. Having multiple regimens with activity, slightly different tolerability profiles, and different administration schedules allows me really to sit there with the patient, make them a partner from day one in their care, learn what their goals are, learn what they hope to accomplish with their treatment, and then be able to individualize and select an appropriate therapy that I think based on my experience and expertise will get them to that goal.

Oncology Data Advisor: That's great. Well, thanks for stopping by to talk about this today.

Dr. Hudson: It was awesome, and thank you for having me.

About Dr. Hutson

Thomas Hutson, DO, PharmD, is the Director of the Urologic Oncology Cancer Research and Treatment Center at Baylor Sammons Cancer Center and the Associate Director and Phase 1 Director for the Sarah Cannon Research Institute. As well, he is a Professor of Medicine at Texas A&M College of Medicine. Dr. Hutson's research interest is with urologic cancers, in which he is involved in many clinical trials and research teams internationally.

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Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of Oncology Data Advisor.