Expert Perspectives of a 67-Year-Old Man with Metastatic HER2+ Gastric Cancer - Episode 5

The DESTINY-Gastric-01 Trial

John Marshall, MD

Dr John Marshall discuss the DESTINY-Gastric01 trial and the implications of the study results to clinical practice for HER2+ metastatic gastric cancer.

John Marshall, MD: The DESTINY-Gastric01 trial has been very important advance in our treatment of HER2-positive gastric and GE [gastroenterostomy] junction cancers or adenocarcinomas. [The study was published] in the New England Journal of Medicine in 2020. We now have a new FDA approval. This is a cool medicine, right? It is trastuzumab, but tied to the trastuzumab is deruxtecan, basically as a loaded smart bomb, is the way I like to think of it. The trastuzumab still tracks to the receptor, which is up-regulated on the tumors. In doing so, yes, it blocks the pathway itself, but it also brings with a payload of a TopA-1 inhibitor, deruxtecan. Chemotherapy is in fact brought to the table. The clinical trial demonstrated a significant response rate in patients who had seen prior HER2-targeted therapy. Primarily done in Asia, and primarily done in third-line therapy, the response rates were good. in the United States, it was approved both in second- and third-line patients.

Now, one of the questions because in other HER2 diseases, we've gotten the routine of repeat HER2 testing. And yes, in this clinical trial, 30% of patients did undergo repeat testing to confirm their HER2 positivity. However, 70% did not. A large proportion of these patients did not undergo repeat testing and were using their baseline testing for HER2 as entry criteria. It’s not a requirement to repeat HER2 testing for this for this treatment. However, it's certainly appropriate to do that if tissue is available or if you can get that testing on circulating samples. Now, the treatment is an IV [intravenous] treatment. It has [chemotherapy-like adverse] effects.

We do have myelosuppression, and there is some nausea and vomiting that is associated with it, so you do need to manage patients through those toxicities. One that has all our antennae up, even though very rare that needs to be monitored is interstitial lung disease. This is often very subtle, as you know. You're used to it in some of your other therapies to track it. However, if patients were getting short of breath or getting cough and you detected interstitial lung disease, typically on a CT scan, the recommendation is to stop the treatment, institute steroids with a higher grade of grade 2 or higher. Do not retry the medicine with lower grade, grade 1 that you picked up maybe on a screening scan. You can treat with steroids reversed and try again at a modified dose. You can rechallenge if the ILD [interstitial lung disease] was very early grade 1. If it is more significant than that, the recommendation is to stop. This comes off more like a chemotherapy, with that ILD as an important toxicity that you need to watch out for. That can occur anytime during the treatment course.

This transcript has been edited for clarity.