Lenvatinib plus pembro for aRCC - update on the CLEAR study

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Published: 12 Sep 2022
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Dr Bradley McGregor - Dana-Farber Cancer Institute, Boston, USA

Dr Bradley McGregor speaks to ecancer about the CLEAR study which explores lenvatinib plus pembrolizumab compared to sunitinib in patients with advanced renal cell carcinoma.

This phase III trial showed statistically significant progression free survival and overall survival benefits, and improved overall response rate with the lenvatinib pembrolizumab combo in the first line setting.

Lenvatinib plus pembrolizumab continued to show a clinically meaningful benefit vs sunitinib, consistent with prior results. A large proportion of patients in the experimental arm completed 2 years of pembrolizumab and continued with lenvatinib monotherapy with ongoing clinical benefit. 

These updated results further support lenvatinib plus pembrolizumab as a standard of care in first line aRCC.

The CLEAR study has been presented already, this was a randomised phase III trial that actually had
three arms. So it looked at the combination of lenvatinib with pembrolizumab versus lenvatinib with
everolimus versus sunitinib and the results have been published which showed a significant
improvement in progression free survival and overall survival for the combination of lenvatinib and
pembrolizumab versus sunitinib. For the lenvatinib everolimus the initial results were there was an
improvement in progression free survival that didn’t translate into overall survival benefit. So further
updates on that have not been forthcoming.

At ESMO just this year we saw an updated analysis with a minimum follow-up of 33 months. Really
what we see at that point in time is that impressive benefit in progression free survival is maintained
and that the combination of lenvatinib and pembrolizumab versus sunitinib has an improvement in
progression free survival across IMDC and MSKCC risk groups and there is no new toxicity signal. In
fact, the complete response rate is the highest we’ve seen for any combination in the modern era,
we’re approaching 17%. So certainly very exciting.

Then when we start looking at the overall survival there continues to be an overall survival benefit with
a hazard ratio just above 0.7. When we start looking at that by the individual IMDC or MSKCC risk
groups it’s limited by small sample sizes so it’s hard to make any definitive conclusions overall. But it
is really encouraging that with extended follow-up we’re still seeing an impressive hazard ratio for
PFS, around 0.4, and an improvement in overall survival across the entire study.
So lenvatinib pembrolizumab continues to remain an option for patients who present with metastatic
clear cell renal cell carcinoma, independent of their risk group. There are no new toxicity signals
identified but it does involve close collaboration with the patient to ensure that the combination can be
delivered safely.