Impact of the CLEAR Trial on Clinical Practice

EP: 1.Current Therapies for Advanced RCC: Options and Challenges

EP: 2.Key Efficacy and Safety Findings from the CLEAR Trial

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EP: 3.Impact of the CLEAR Trial on Clinical Practice

EP: 4.Updates on CLEAR from ASCO 2021

EP: 5.The Future of Therapy for Advanced RCC

Robert J. Motzer, MD: What are the implications of [the CLEAR trial] efficacy and safety findings for clinical practice? My impression is that lenvatinib plus pembrolizumab is a good contender as a first-line choice for patients with advanced renal cell carcinoma [RCC]. The efficacy data that we have seen with regard to the median progression-free survival of 23.9 months is the longest that we have seen in any of the phase 3 trials on RCC, and the objective response rate of over 70% was the first time we have crossed that bar. What was also impressive was the duration of response and the complete response rate of 16%. It’s difficult to make definitive comparisons across studies. There are many limitations including the time that the study was conducted, the population, and the way efficacy and safety are assessed, but certainly lenvatinib plus pembrolizumab is a good choice for a first-line therapy for patients with advanced RCC. Now, currently this combination has not yet received regulatory approval in the United States or Europe, but it certainly has gained a position in the NCCN [National Comprehensive Cancer Network] treatment guidelines for RCC as a level I preferred regimen in the first-line therapy for RCC along with the other TKI/IO [tyrosine kinase inhibitors / immuno-oncology] combinations of cabozantinib and nivolumab exit the pembrolizumab and ipilimumab and nivolumab, specifically in the intermediate- and poor-risk group for that population. Who would be a good choice for lenvatinib and pembrolizumab? I think certainly patients with favorable risk tumors, and also patients that have rapidly advancing disease in which you really want to ensure an immediate response to therapy. For others in the intermediate- and poor-risk group, there is a debate in terms of whether the role or rationale for TKI/IO combination versus ipilimumab and nivolumab since the data with ipilimumab and nivolumab are more mature and show a durable response in patients with intermediate- and poor-risk tumors over a long time. I think with regard to the TKI/IO combinations, in particular lenvatinib and pembrolizumab, more follow up is needed so we get a sense for whether we are seeing the same degree of durable responses for lenvatinib plus pembrolizumab as we are for the IO combination of ipilimumab and nivolumab.

This transcript has been edited for clarity.