Incorporating Data from the CLEAR Trial into Clinical Practice

Video

Experts discuss how data from the CLEAR trial affects the management of advanced renal cell carcinoma in their clinical practices.

Brian Rini, MD: How have you incorporated this into your practice? I don’t know if you’re an I/O–I/O [immuno-oncology] person or an IO–TKI [tyrosine kinase inhibitor]. If you’re an I/O–TKI, for those patients, do you give those regimens too? Are you choosing these over others? How are you making those decisions?

Mehmet Asim Bilen, MD: To me, it’s still a tough discussion, Brian. We see all those patients in our clinical practice, and those conversations are long because we don’t have only 1 option; we have several. Unless we have a good predictive biomarker, I don’t think our job is going to be simpler soon. Overall, when I see a patient, try to make that big decision. Should I go I/O–I/O or I/O–VEGF? The advantage for I/O–I/O, especially if they’re on maintenance immunotherapy, is that they have a good quality of life. There’s no way to beat that quality of life with any VEGF inhibitors vs I/O–TKI combinations, it tends to be a higher response rate. If we have a patient in whom we want to achieve rapid response and tumor reduction, they’re very appealing. Among those 3 options—pembrolizumab plus axitinib, nivolumab plus cabozantinib, and lenvatinib plus pembrolizumab—all 3 look great, and all 3 look effective. I don’t have a clear sense which should be my winner. All of those are effective for patients with kidney cancer.

Moshe Ornstein MD: The first thing we look at is the high-level results, which have to do with response rate, PFS [progression-free survival], complete response rate, and hazard ratio for survival. When I look at the results of the CLEAR trial, I’m looking at the high-level results of lenvatinib and pembrolizumab. I ask myself, “What would I have wanted to see from this trial,” because it’s the fifth or so of the I/O–based combinations in frontline RCC [renal cell carcinoma]. In other words, we’ve already seen ipilimumab and nivolumab, we’ve seen axitinib and pembrolizumab, we’ve seen axitinib avelumab, and we’ve seen cabozantinib and nivolumab. All those had some differences but a lot of similarities, and the field was waiting for this 1 to come out. If we were to say, before the trial came out, that the objective response rate would be over 70%, that the complete response rate would be over 15%, 16%, that the PFS would be close to 2 years, those numbers for many would be considered practice changing. Obviously, there’s a role for all the I/O–TKIs, but from a high-level perspective and cross-trial comparisons, of course, there are always challenges.

At the end of the day, when you line up the PFS response rate, the complete response rate for this trial compared with some of the other ones, the benefits seem to tilt in this direction. For the average patient who has de novo metastatic RCC that has yet to be treated, I tend to prefer this regimen when I’m choosing an I/O–TKI. For me, though, the first thing I think about is if this is a patient, I can give an I/O–I/O, to or am I choosing an I/O–TKI? Within the I/O–TKI regimens, it’s important for that patient to have a response right up front. It’s important to have a long PFS before we need to move to something else. It’s an embarrassment of riches these days, but that’s how I look at it.

Transcript edited for clarity.

Recent Videos
Hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, discuss presentations at ESMO 2025 that may impact bladder, kidney, and prostate cancer care.
Experts weigh in on tumor-informed testing, false positives, relevant trial data, and other key concepts related to circulating tumor DNA.
Ongoing studies in kidney cancer aim to explore determinants of immune-related adverse effects and strategies for mitigating them.
Machine learning-based approaches may play a role in further understanding of how somatic alterations influence responses or resistance to therapy.
Data from a first-in-disease trial assessing a personalized cancer vaccine in RCC require validation at a larger level, according to David Braun, MD, PhD.
Experts highlight methods for optimally treating patients with genitourinary cancers harboring variant histologies at World GU 2025.
Considering which non–muscle-invasive bladder cancer cases may be cured by surgery alone may help mitigate overtreatment in this patient group.
Related Content
Updated results from SunRISe-4 support further investigation of the gemcitabine intravesical system plus cetrelimab in MIBC.

Gemcitabine Intravesical System Combo Shows High pCR Rate in MIBC

Kristi Rosa
October 17th 2025
Article

Updated results from SunRISe-4 support further investigation of the gemcitabine intravesical system plus cetrelimab in MIBC.

Experts highlight anticipated sessions at the 2025 ESMO Congress, including those on the PSMAddition and EV-303 trials.

Exploring the ESMO 2025 Presentations That May Shift GU Oncology

Manojkumar Bupathi, MD, MS;Benjamin Garmezy, MD
October 16th 2025
Podcast

Experts highlight anticipated sessions at the 2025 ESMO Congress, including those on the PSMAddition and EV-303 trials.

Perioperative Durvalumab/NAT Chemo Does Not Improve HRQOL in MIBC

Perioperative Durvalumab/NAT Chemo Does Not Improve HRQOL in MIBC

Ben Saylor
October 17th 2025
Article

New findings reveal that adding durvalumab to neoadjuvant chemotherapy does not enhance HRQOL in muscle-invasive bladder cancer patients.

Prospective data observed with the gemcitabine intravesical system may be superior to prior reports of other therapies in BCG-unresponsive NMIBC.

Gemcitabine Intravesical System Offers Tremendous Benefits in NMIBC

Gary Steinberg, MD
September 29th 2025
Podcast

Prospective data observed with the gemcitabine intravesical system may be superior to prior reports of other therapies in BCG-unresponsive NMIBC.

The safety profile of the atezolizumab with Bacillus Calmette-Guérin in NMIBC was consistent with that of each individual agent.

Atezolizumab Did Not Improve EFS in Non–Muscle-Invasive Bladder Cancer

Sabrina Serani
October 17th 2025
Article

The safety profile of the atezolizumab with Bacillus Calmette-Guérin in NMIBC was consistent with that of each individual agent.

Anticipated data from the ESMO Congress 2025 may have implications for standards of care across prostate and bladder cancer groups.

How Will ESMO 2025 Data Shape the Future of Genitourinary Cancer Care?

Russ Conroy
October 15th 2025
Article

Anticipated data from the ESMO Congress 2025 may have implications for standards of care across prostate and bladder cancer groups.