Chung-Han Lee, MD, PhD, Discusses Biomarkers for Response in RCC With Pembrolizumab Plus Lenvatinib

In an interview with CancerNetwork® during the 2022 Genitourinary Cancers Symposium,Chung-Han Lee, MD, PhD, assistant attending physician for the Genitourinary Oncology Service at Memorial Sloan Kettering Cancer Center in New York, discussed using biomarkers for response prediction in patients being treated with lenvatinib (Lenvima) plus pembrolizumab (Keytruda) for metastatic renal cell carcinoma in the KEYNOTE-146 study (NCT02501096). The study found there were no statistically significant associations between gene signatures and outcomes in patients who are receiving treatment in the second-line setting.

Transcript:

The KEYNOTE-146 study in an unselected population showed very high objective response rates, depending on the cohort, in the 50% to 70% range, including people who were naïve [to and pretreated with immuno-oncology agents]. In terms of biomarker studies, we later did go back to see whether there were any biomarkers that could predict outcomes with the combination of lenvatinib plus pembrolizumab. Historically, there have been biomarker [investigations] in the front-line space, however, none of this has actually been well studied for any of the TKI [tyrosine kinase inhibitor] or IO combinations.

What we have demonstrated in this study is unfortunately, the biomarkers that were predictive for treatment-naïve patients didn’t seem to correlate well to later lines of systemic therapy. Right now, we’re still doing further studies to better understand why that was the case, and whether it’s the tumors that have changed after they’ve gone through multiple rounds of systemic therapy or the biomarkers that preexist are just not robust enough to [adapt] to these types of changes. As a result, we would say that lenvatinib plus pembrolizumab remains a very active combination, regardless of any biomarker stratification.

Reference

Lee CH, Rasco D, Rao A, et al. Association between biomarkers and clinical outcomes of lenvatinib + pembrolizumab in advanced renal cell carcinoma (RCC): Results from Study 111/KEYNOTE-146. J Clin Oncol. 2022;40(suppl 6):137. doi: 10.1200/JCO.2022.40.6_suppl.375