The CLEAR Trial: Lenvatinib Plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma - Episode 5

Subgroup Analyses of the CLEAR Study in mRCC

An overview of data demonstrated by other investigational studies of lenvatinib plus pembrolizumab as frontline therapy for metastatic renal cell carcinoma.

Chung-Han Lee, MD, PhD: Since the initial presentation of the CLEAR study at ASCO GU [American Society of Clinical Oncology Genitourinary Cancers Symposium] 2021, there have been several subgroup analyses to further understand the regimen. At ASCO GU, looking at the quality-of-life data that were absent from the original CLEAR study, the authors noted that the quality of life on lenvatinib plus pembrolizumab was fairly similar to what was seen with sunitinib. This has waged some of the initial concerns about the absence of the data at the initial presentation. It also fills in some of the knowledge gaps and counters some of the reputation that lenvatinib is a relatively difficult regimen, which it gained during the earlier phase 2 study of lenvatinib plus everolimus. It was reassuring for us to see that when people were treated on lenvatinib plus pembrolizumab, the quality of life was quite similar to sunitinib in that phase 3 study.

Furthermore, there was also a separate analysis looking at depth of response and overall survival. What the authors had seen is that the depth of response did correlate with improved overall survival, meaning people who had deeper responses overall did better. For patients who were treated on the CLEAR study on the sunitinib arm, now that we’ve gone further out, it remains a matter of debate on what they would be necessarily receiving next. A lot of that depends on access to drugs. For patients who are on single-agent TKIs [tyrosine kinase inhibitors], there’s broad access to immune checkpoint inhibitors. Immune checkpoint inhibitors, either as monotherapy or combination, would be very appropriate next choices. However, in certain countries, in which immune checkpoint inhibitors are not yet available, a lot of those patients would be receiving secondary TKIs.

Transcript edited for clarity.