Improving Survival in Metastatic Urothelial Cancer - Episode 3

Value of PD-L1 Testing in Metastatic Urothelial Cancer


Jeanny Aragon-Ching, MD: At what point do we test for PD-L1? I usually test early. You can do this as part of a genomics panel. There are certain platforms, like Foundation Medicine, that automatically test for PD-L1. I mentioned earlier that you do not necessarily need to test PD-L1 when using second-line therapy and beyond for checkpoint inhibitors, but the utility of PD-L1 testing is for first-line therapy for metastatic urothelial cancer, especially those who are cisplatin-ineligible.

For those who are cisplatin-eligible, chemotherapy remains the standard of care. In fact, even for those who are ineligible who are otherwise carboplatin-eligible, chemotherapy is still and remains the standard of care. There are, of course, areas of contention. Some people would test only at the time when there are no other options. For the most part, I believe testing early would be the way to go, so that we have that information early enough on hand.

Which tests do we use to determine PD-L1 status? This is highly dependent on each institution—your practice, as well as the comfort level for the pathologist. It’s really dealer’s choice. There are also certain FDA-approved tests that accompany the use of certain drugs. For atezolizumab, it is recommended to use the VENTANA SP142 assay. Their definition of positive also differs. For the VENTANA SP142 assay, the PD-L1 expression of greater than or equal to 5% for the immune cell is considered positive.

For pembrolizumab, they use a different assay. They use the 22C3 antibody, and they’re looking for a combined positive score of more than 10. For avelumab in the JAVELIN Bladder 100 trial, they use SP263 assay; it really varies across platforms. There has been no real great standardization of all these assays, so I would say it’s up to whatever patients, or really physicians and institutions, are comfortable with and whatever drug they mean to use.

Shilpa Gupta, MD: For our advanced urothelial cancer patients, we are getting next-generation sequencing because about 10% of patients may exhibit FGFR3 mutations, for which we have an available drug called erdafitinib. In PD-L1 testing, it is routinely done as a part of these tests to guide therapy for patients who cannot get platinum as first-line therapy. As far as molecular subtyping goals, that’s still an active area of research.

Transcript Edited for Clarity