Importance of PD-L1 Expression in Kidney Cancer

Toni Choueiri, MD:PD-L1 testing probably is the most used and, to some degree, abused biomarker in immuno-oncology—by far. And it has a lot of variables: What antibody? Is it an immune cell, tumor cell? Who is staining it? And in kidney cancer, specifically, we know that for PD-L1—positive patients with metastatic RCC, it’s the worst. We have shown that from previous studies using VEGF tyrosine kinase inhibitors.

In nivolumab-treating patients in the CheckMate-025 trial, the study versus everolimus, PD-L1 testing confirmed prognostic but not predictive values. This means the benefit of nivolumab was irrespective of PD-L1 testing. And here we are on CheckMate-214—there’s a different signal. Patients who were PD-L1—positive or PD-L1–negative had the overall survival benefit—both of them—but the benefit was much more pronounced in patients with PD-L1–positive disease.

So, at this time, the story is evolving. It’s still very intriguing. The primary endpoints that were met were independent of PD-L1 testing. I think this may become more relevant perhaps with other combinations rather than the nivolumab/ipilimumab combination. To me, based on the CheckMate-214 results—the large frontline study of nivolumab/ipilimumab—this brings back PD-L1 to the equation, perhaps not yet for testing in practice but at least for us clinical investigators and clinical trialists. We should just take it in consideration sometimes, stratify for future trials, or at least collect the tissue and look how patient outcome is based on PD-L1 testing. At some point, we almost drop that.

Transcript edited for clarity.