The Phase 3 CLEAR Trial: Lenvatinib Plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma - Episode 4

Updates on CLEAR from ASCO 2021

Dr Motzer discusses data from the CLEAR trial that were presented at ASCO 2021.

Robert J. Motzer, MD: There have been other sub-analyses that were presented at this year’s ASCO [American Society of Clinical Oncology Annual Meeting], one of which was the patient-reported quality of life or health-related quality-of-life studies that were performed from the CLEAR trial. These were questionnaires that patients filled out according to established scales to assess quality of life. In summary, the score showed that patients with lenvatinib plus pembrolizumab had similar or better quality of life compared to those with sunitinib. Those treated with lenvatinib plus everolimus had similar or worse quality of life scores compared to patients with sunitinib. Again, that particular analysis was related to health-related quality of life analysis. Lenvatinib plus pembrolizumab appears to be the winner and this was based on the quality-of life studies plus the efficacy that was established in the trial and the safety profile. These studies supported that as a first-line regimen. There were other sub-analyses that were done as well at ASCO that were reported. One was to look at the depth of response. Lenvatinib plus pembrolizumab is associated with deep responses in addition to a higher response rate. These deep responses correlate with longer progression-free survival. There was also a sub-study that looked at subsequent therapy for patients on the CLEAR trial, and really the gist of that was that the patients who were on the sunitinib and on lenvatinib plus everolimus frequently at time of progression crossed over and received immunotherapy. This is certainly a factor in terms of looking at the survival benefit for lenvatinib plus pembrolizumab which contains IO [immuno-oncology] therapy [the] in first-line and also in comparison to sunitinib plus lenvatinib plus everolimus arms. In that sub-analysis, there were more patients on the sunitinib arm that crossed over and received checkpoint inhibitor as second- or third-line therapy. We feel that that probably is the reason why there was not a survival benefit in the lenvatinib plus everolimus versus sunitinib arm. Many of the patients who progressed on either 1 of those 2 arms were successfully salvaged with IO therapy, and to me that really brings home the importance and the role for checkpoint inhibitor therapy in [the] treatment of advanced RCC [renal cell carcinoma] preferably in combination for first-line therapy with either IO/IO combinations like ipilimumab and nivolumab or TKI [tyrosine kinase inhibitor]/IO combinations, but certainly in patients who have been treated with TKI monotherapy or with other regimens to gain access to checkpoint inhibitors in second- or third-line therapy.

This transcript has been edited for clarity.