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Dr. Cleary
This is CE on ReachMD, and I'm Dr. James Cleary. Now, let's examine a patient case example, so we can apply the recent clinical trial data to treatment selection for our patients with HER2-negative PD-L1 positive gastroesophageal cancer.  

So the first patient I wanted to give is a patient with newly diagnosed gastroesophageal junction cancer that's metastatic. This patient is a 60-year-old woman. The patient has a tumor that has a PD-L1 CPS score of 25 but also is claudin 18.2 positive. 

So the reason I gave this example is the PD-L1 with a CPS score of 25, that's actually quite high. So in a case like that, even though the claudin 18.2 is positive, I really prefer to use PD-1 antibodies here. So for a patient like this that has a tumor that has a CPS score of 25 and is claudin 18.2 positive, I'm going to treat that patient with FOLFOX/nivolumab, FOLFOX/pembrolizumab, or FOLFOX/tislelizumab. 

In another example, in a patient with a patient with metastatic gastroesophageal cancer, 60 years old, who has a PD-1 negative tumor but a claudin 18.2 positive tumor, well, that's a great use for zolbetuximab. So in this patient that's PD-L1 negative but claudin 18.2 positive, this is super because this patient—anti-PD-1 antibodies aren't approved in patients with PD-L1 negative tumors. But fortunately for this patient, they're claudin 18.2 positive so for this patient, I'm going to treat them with FOLFOX/zolbetuximab. And again, I want to remind you that zolbetuximab can cause more nausea, so please give extra anti-nausea medications and make the patient aware. 

And then the final case—and this is a tough one, and it’s one I struggle with—is a 60-year-old patient with metastatic gastroesophageal cancer, who has a tumor with PD-L1 CPS score of 6 but is claudin 18.2 positive. Now, this is an example—we don't have clinical trial data to guide us, and I will say there's clinical trials going on right now that are combining chemotherapy, PD-L1, and zolbetuximab, so hopefully we won't have this situation in the future. But for now, in a patient with a PD-L1 CPS score of 6 tumor that's also claudin 18.2 positive, my practice is to give FOLFOX and an anti-PD-1 antibody. The reason for that is, again, I think patients want therapies that are going to have a very durable effect. And at least in oncology, where we've seen the most durable effects have been PD-1 antibodies. And because of that, I give FOLFOX anti-PD-1 antibodies to these patients. 

What these three cases show is the importance of biomarker testing in guiding our decision-making in gastroesophageal cancer. So it's really important to talk to your pathologists about making sure that for all of your gastroesophageal cancer patients you're getting IHC, looking at mismatch repair IHC, HER2 IHC, PD-L1 IHC, and claudin 18.2 IHC; because those IHC tests are really going to guide how you treat your patients in the first-line setting. 

In addition to those four biomarkers, I do immunohistochemical testing on, I also like to get next-generation sequencing testing on all my patients, as that could guide therapy in second and third line.

Thank you very much for listening.

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