Lenvatinib and pembrolizumab show promising efficacy in first-line treatment of aRCC

Prof Viktor Grünwald - University Hospital Essen, Essen, Germany

Basically we looked into the CLEAR study and the CLEAR study investigated the use of lenvatinib and pembrolizumab versus sunitinib in previously untreated patients that had metastatic disease from kidney cancer. The pivotal trial showed superior outcomes for the combination with regard to response, progression free survival and overall survival.

So what we really looked into at this very meeting is we focussed on whether tumour burden had an impact on clinical outcome in these patients.

What was the study design?

Basically what we used is the final dataset analysis with the cut point of July of 2022 of the CLEAR study which allowed for four years of median overall survival. That’s a very mature set. We then built up quartiles of the baseline sum of target lesions for those patients. So we had four different groups of patients with quartile four being the one having the most and heaviest tumour load. So that’s how we split the groups and looked into the outcome parameters.

What were the results of this study?

What we really found was that when you look into the clinical activity in regard to the tumour burden of patients, we have seen a similar efficacy for lenvatinib/pembrolizumab across all those four different subgroups. The only thing that we also recognised was that patients that have a heavy tumour load, they have a lower fraction of patients that receive prior nephrectomy and also a higher chance of being intermediate or poor risk. Those two components are known to have prognostic impact so they are associated with worse outcome, worse overall survival. That’s what we also have seen in our study where we didn’t see major differences in the overall survival but patients with a higher tumour burden had the worst outcome in that setting.

What is the clinical impact of these results?

What it tells us is that lenvatinib/pembrolizumab is working irrespective of the tumour load that patients have at the time of start of treatment. That’s quite reassuring. It’s one of the treatment options that we have in first line for kidney cancer patients available.

What is next for this study?

For the study we will continue to explore subgroups and to try to better understand from a clinical perspective what does it mean in the clinic and how can we make use of that combination best. So that’s also something that we covered at this very meeting – we fitted in a meta-analysis, network meta-analysis on the topic of first-line agents and availabilities and how they performed. So what it turned out to be is that lenvatinib/pembrolizumab confirmed its activity being one of the most potent immune combinations in first line. However, when it comes to the point that when we look into overall survival it seems to be that all those combinations seem to be in the same range. That’s also quite reassuring that combinations should be used in first line and they improve the overall survival of patients if you use a more intense therapy.