Charles S. Fuchs, MD, MPH, director, Yale Cancer Center, physician-in-chief, Smilow Cancer Hospital, 2017 Giant of Cancer Care in Gastrointestinal Cancer, discusses immunotherapy in gastric cancer.

Better therapies are needed for patients with advanced gastric cancer, says Fuchs, and immunotherapy could be an option.

PD-L1 expression is seen in gastric cancer, suggesting that immunotherapy agents—such as pembrolizumab (Keytruda)&mdash;would be effective in this commonly occurring disease.

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Dr. Fuchs Discusses Immunotherapy in Gastric Cancer

Charles S. Fuchs, MD, MPH, director, Gastrointestinal Cancer Center, Dana-Farber Cancer Institute, discusses targeting angiogenesis in the treatment of gastric cancer.

In the AVAGAST trial, patients were randomized to chemotherapy or chemotherapy plus bevacizumab in the frontline. Results from the trial indicated a benefit to progression-free survival (PFS) and response, but no significant effect on overall survival (OS).

Fuchs says he was involved in a randomized study of ramucirumab, a monoclonal antibody against VEGFR2, compared with placebo in the second-line. Treatment with ramucirumab demonstrated significant improvement to OS and PFS, as well as a trivial toxicity profile.

Dr. Fuchs on Angiogenesis in Gastric Cancer

Charles S. Fuchs, MD, MPH, director, Gastrointestinal Cancer Center, Dana-Farber Cancer Institute, discusses the use of aspirin for the prevention and treatment of colorectal cancer.

Studies have suggested that aspirin can reduce the risk of colorectal polyps or cancer, Fuchs says, providing level 1 evidence for aspirin as a preventative agent. More recently, researchers have looked to see if aspirin can provide benefit for patients with established colorectal cancer.

Several trials have collected information on aspirin use in patients who have started chemotherapy for stage 1, 2, or 3 colorectal cancer. In all of these observational studies, those patients who reported aspirin use had significant improvement in cancer-free survival. The next step, Fuchs says, is to define biomarkers and understand the mechanisms of aspirin.

It is widely believed that one target for aspirin is cyclooxygenase-2 (COX-2), a marker that affects an increased proliferation in cancer cells. As approximately two-thirds of colon cancers overexpress COX-2, the question presented itself as to whether or not aspirin would be more effective in a tumor that overexpressed COX-2.

In the laboratory, Fuchs says, it was seen that in those two-thirds of patients whose tumors overexpressed COX-2, they saw significant improvement in survival. Conversely, if a tumor did not overexpress COX-2, the benefit of aspirin was minimal.

As all of the studies looking at aspirin in colorectal cancer have been observational, Fuchs says there is a need for randomized trials like CALGB 80702. In this trial, patients who have been resected for stage 3 colon cancer will receive chemotherapy and will be randomized to a COX-2 inhibitor (not aspirin). This trial aims to answer the question as to whether COX-2 inhibition can contribute to survival benefit in this space.

Dr. Fuchs on Aspirin for the Treatment of Colorectal Cancer

Charles S. Fuchs, MD, MPH, director, Gastrointestinal Cancer Center, Dana-Farber Cancer Institute, discusses the potential of targeting the c-MET receptor to treat gastrointestinal cancers.

Fuchs says c-MET is an important receptor that drives cell proliferation. Results from laboratory tests have shown that certain gastric cancers overexpress c-MET. When c-MET inhibitors are given to patients who have this kind of cancer, cell death occurs.

A randomized phase II of an agent (AMG102) targeting the c-MET ligand hepatocyte growth factor (HGF) showed that patients who received chemotherapy plus the antibody did better than patients who received chemotherapy alone. Fuchs says the benefit was primarily among the individuals who had c-MET-overexpressing gastric cancer. The overexpression provides a practical biomarker.

Fuchs says that about 45% of patients have c-MET-overexpressing gastric cancer.

Charles S. Fuchs, MD

Articles

Dr. Fuchs Discusses Immunotherapy in Gastric Cancer

Dr. Fuchs on Angiogenesis in Gastric Cancer

Dr. Fuchs on Aspirin for the Treatment of Colorectal Cancer

Dr. Fuchs on Targeting c-MET to Treat Gastric Cancers