Expert: Combination of Lenvatinib, Pembrolizumab Outperformed Sunitinib in the Treatment of Advanced RCC

Pharmacy Times interviewed Viktor Grunwald, MD, PhD, professor, Interdisciplinary Genitourinary Oncology, University Hospital Essen, on the post-hoc analysis of tumor response by baseline characteristics of the metastases from the phase 3 CLEAR (Study 307)/KEYNOTE-581 trial (NCT02811861), which evaluated lenvatinib (Lenvima; Eisai) plus pembrolizumab (Keytruda; Merck) vs sunitinib (Sutent; Pfizer) for the first-line treatment of patients with advanced renal cell carcinoma. Results from the trial were presented at the 2023 European Society of Medical Oncology (ESMO) Congress.

Pharmacy Times: What did the CLEAR trial show regarding lenvatinib in combination with everolimus or pembrolizumab compared to sunitinib alone in improving PFS as first-line treatment in participants with advanced RCC?

Viktor Grunwald, MD, PhD: So basically, the CLEAR study investigated the use of lenvatinib in combination with everolimus or pembrolizumab vs sunitinib. Basically, what it showed is that the combination of lenvatinib and pembrolizumab has been superior to the use of sunitinib in terms of responses, in terms of progression free survival and overall survival. So, it really outperformed sunitinib, which was the former standard of care. And it's now one choice of our first line treatment options for the treatment of kidney cancer.

"Basically, what it showed is that the combination of lenvatinib and pembrolizumab has been superior to the use of sunitinib in terms of responses, in terms of progression free survival and overall survival." Image Credit: © Axel Kock - stock.adobe.com

Pharmacy Times: What is the burden of disease on patients with advanced RCC, and what are the implications of these results for patients with advanced RCC?

Grunwald: So advanced RCC is really a mixture of metastatic or locally advanced disease. But in principle, what it means is that those patients are not amenable or not candidates for local therapies, meaning surgery or radiotherapy. So, we offer them medical treatments. So, the burden of disease is high because it implies that patients die of their disease.

With the options that we have nowadays, these are life prolonging agents, and it's a very good option to treat patients.

Pharmacy Times: Would you discuss further the subgroup analysis conducted on the CLEAR trial?

Grunwald: So, in this subgroup analysis, so postdoc analysis to be performed, we investigated whether the tumor response by metastatic site did make the difference. And I think it's important to do this type of analysis because, in previous settings, we looked into patient cohorts that had the phenotype of liver metastasis, lung metastasis, or bone metastasis, and we looked at the overall tumor shrinkage in the metastatic sites. So, meaning, we grouped by metastatic site, but we investigated by the overall objective response rate.

Thinking about the patients sitting in front of you, for that patient, you will see a similar response rate in his or her liver metastasis, and I think it makes a difference, because I mean, that's how you counsel, and you can use this type of information. So that's why we really looked into the target lesions by organ sites, and that the tumor shrinkage in metastasis confined to the liver, lung, or bone would behave similarly as the ITT population. And that's really what we investigated, and we what we have seen is that the tumor shrinkage that we that we showed did occur to the same degree in magnitude in favor of the combination of [lenvatinib and pembrolizumab] vs sunitinib across all those metastatic sites basically. So it reassures the use of [lenvatinib and pembrolizumab], and it shows that the productivity that we have seen in the overall population is also occurring by each disease site.

Pharmacy Times: Closing thoughts?

Grunwald: So, in principle, I mean, this was the first step to really investigate deeper the role of tumor shrinkage in patients or metastasis by organ sites. And I think it's quite important to understand what are the drivers of response and whether a particular metastatic pattern would show a detrimental effect or would be in favor of a specific type of therapy and something that I think that we also have to investigate is really whether the tumor load or tumor burden is also associated with the with the type of response that we're seeing. So, I think, there's more to discover in the datasets that we have already from the pivotal trials.