PD-L1 guideline panels hustle to keep pace with drug advances

Create PDF

Dr. Broaddus

One common pitfall, for example: “There’s a prevalent opinion out there that if two tests overlap, if they’re essentially synonymous, you only have to do one. That’s not really the case. There’s some very good published evidence in peer-reviewed literature that says testing isn’t always concordant and the discordan­ces can be very, very important. It’s not common, but a tumor may have high levels of MSI by a PCR test but have intact expression of MMR protein by IHC. So the other challenge is going to be: If we’re going to recommend just one test, what test will it be? Will it be immunochemistry? Will it be the PCR-based assay?”

Pathology will need to rethink traditions to adjust to the new scope of pembrolizumab, and that will take time, he thinks. “The pathology world is very familiar with these assays to screen for hereditary cancer syndrome, but they’re not used to thinking of them as a way to screen for a drug. The GI pathologists will have tons of experience with this, but other pathologists will have little to no experience. Now, all types of pathologists will need to gain experience in how to interpret a PCR-based slide test and IHC assays for mismatched repair proteins.” Many pathology residents, even after four or five years of training, have also never seen these assays before, he adds. “So that’s a key gap we need to address in the discipline of pathology—to get our residents in training more exposure to this type of diagnostic testing—because it’s not going to decrease anytime soon.”

“We see in pathology a lot of different treatment approaches that create excitement for six months and then kind of go away. This is something that keeps building and new advances keep coming, so I think this is a treatment approach that will keep its steam up for at least the next few years,” Dr. Broaddus says.

Dr. Sholl agrees. “There has definitely been a change of tone in the FDA’s way of looking at these drugs. That, in and of itself, is quite a tide change.” But caution will be needed because the full story isn’t known yet, she says. “Ultimately we need to be examining these cohorts of patients very carefully. The FDA’s approval of pembrolizumab for DNA mismatch repair deficiency across all tumor types is based on, outside of colon and endometrial cancers, a very low number of tumors. So the data is really still accumulating. And we’ll just need to keep studying it.”
[hr]

Anne Paxton is a writer and attorney in Seattle.