Dr Ilson Talks Current Role of Immunotherapy in GEJ, GI Cancer- Part II

In part 2 of this video series, David Ilson, MD, PhD, Memorial Sloan Kettering Cancer Center, discusses approvals and advancements in the immunotherapy related treatment space, presented at the 2021 Great Debates and Updates in GI Malignancies Annual Meeting. 

Transcript

Hi, I am Dr. David Illson. I am a GI medical oncologist at Memorial Sloan Kettering Cancer Center where I am attending physician and professor of medicine. I am going to comment today on an update on immunotherapy treatments in esophageal gastric cancer.

I just want to comment on the advance of immunotherapy-related drugs in targeted agents. In the HER2 space, there is an ongoing trial of trastuzumab chemotherapy with or without pembrolizumab in HER2-positive GE junction and gastric adenocarcinomas based on very promising Phase II data.

That trial is ongoing to see whether there is a benefit for trastuzumab plus checkpoint inhibitor in the first-line treatment of HER2-positive esophageal gastric cancer. There are some other interesting agents in this space. The drug margetuximab, which was recently approved for breast cancer, that is a HER2-targeted antibody which also have enhancements in antibody-dependent cytotoxicity.

That is now being moved up earlier line in esophageal gastric cancer that is HER2-positive in a randomized trial as well.

Some provocative data targeting the FGF receptor in patients that were IHC-positive for the FGF receptor, 30% of patients with GE junction gastric adenocarcinoma that were screened on this trial were positive by IHC for FGFR over expression. These were patients that were also HER2-negative.

The trial bemarituzumab which blocks and targets the FGFR receptor in a randomized Phase II trial was shown to improve survival added to first-line FOLFOX in FGFR-over-expressing patients. This is an antibody in addition to blocking the FGF receptor that may also lead to enhanced ADCC. There may be an immunologic mechanism to this antibody as well.

Lastly, I want to comment on targeting the claudin pathway which is a gap junction protein that is over-expressed in gastric adenocarcinoma.

There is an ongoing trial of the monoclonal antibodies, zolbetuximab, which targets this protein added to chemotherapy in the first-line treatment of GE junction and gastric adenocarcinomas that overexpress the claudin protein which about 30% of patients are high over-expresses of this target.

This is an antibody also that may lead to immune cell recruitment. It is thought to be its main mechanism of action.

In addition to checkpoint inhibitors potentially moving into first-line treatment, adjuvant treatment, we have exciting leads of other immunotherapy-related drugs targeting other pathways including HER2, the claudin pathway, and FGF that are moving forward in randomized trials.

It is an exciting time, and there is now a clear role for immunotherapy drugs emerging in the treatment of the esophageal gastric cancer.