The Evolving Role of Immunotherapy for Gastrointestinal Cancers

Raymond Wadlow, MD, is an oncologist at Inova Schar Cancer Institute. He is board-certified in Medical Oncology and Internal Medicine and has a special interest in gastrointestinal oncology. 

Immunotherapy is a relatively new type of cancer therapy — and for some cancers, it has been a game changer. Unfortunately, it’s been a bumpier road for immunotherapy in the treatment of gastrointestinal (GI) cancers. That’s starting to change, however, as the medical community learns more about how to optimize these medications.

What Is Immunotherapy?

Immunotherapy harnesses a person’s own immune system to fight cancer. The immune system’s job is to spot invaders like bacteria, viruses or cancer cells and get rid of them. But cancer cells have evolved ways to hide from the immune system. This sneaky ability can allow cancer to grow and spread unchecked.

Immunotherapy drugs work in a variety of ways. Essentially, though, they work by boosting a patient’s immune system to attack the cancer. These drugs have been extremely effective for some patients with certain types of cancer, such as melanoma. However, they’ve been less successful in treating gastrointestinal cancers, including gastric, esophageal, pancreatic, liver, gallbladder and intestinal cancers.

Colon Cancer Immunotherapy

Recently, researchers discovered an important exception to that rule. In 2020, a large clinical trial showed that an immunotherapy drug called pembrolizumab (Keytruda®) is effective in a subset of patients with newly diagnosed stage 4 colon cancer that has metastasized, or spread, to other parts of the body. Patients whose cancers have a characteristic called microsatellite instability, or MSI, seem to respond well to this drug.

In fact, pembrolizumab was more effective than chemotherapy in these patients. The researchers who led the study concluded that it should be the preferred treatment option in patients with metastatic stage 4 colon cancer with MSI markers. This has changed the way oncologists are caring for that subset of patients, including those being treated at Inova.

Immunotherapy Research: New Strategies for GI Cancer

This study was an important development, since it marks the first real breakthrough for immunotherapy as a treatment for colorectal cancer. Unfortunately, only about 10% of people with stage 4 colon cancer test positive for the MSI marker. For the majority of people with gastrointestinal cancer, immunotherapy hasn’t been as effective as traditional treatments such as chemotherapy and radiation — at least, not yet.

Cancer researchers at the Inova Schar Cancer Institute and others, are looking for new and better ways to use immunotherapy in patients with GI cancers. One strategy involves identifying new markers like MSI that could help us pinpoint which patients are likely to respond to which treatments.

Another promising strategy could be to combine multiple drugs. One difficulty in GI cancers is that they are what scientists call “immunologically cold” — they don’t seem to activate the immune system at all. That means drugs like pembrolizumab that boost the immune response don’t have much effect, since there are no immune cells near the tumor to begin with. To get around that problem, researchers are looking for drugs that might draw immune cells into the tumor’s environment. Once the cells are there, immunotherapy drugs such as pembrolizumab could be used to crank up the immune attack on the tumor.

Benefits of Immunotherapy

Immunotherapy has been a really important advance in the way we treat cancer. And there are good reasons to continue this line of research:

• Immunotherapy may work better. When you kill cancer cells with chemotherapy, some cells are often left behind. They can develop resistance to the chemotherapy and grow back. There is evidence to suggest that some cancers may be less likely to become resistant to immunotherapy drugs.
• Side effects are usually manageable. Immunotherapy can sometimes produce serious side effects if the immune system attacks healthy tissues, such as the skin, lungs or liver. But in general, immunotherapy side effects are manageable. For many patients, they are milder than the side effects associated with chemotherapy.

While immunotherapy isn’t yet a sure thing for treating GI cancers, we’re optimistic that research is swiftly moving in the right direction. At Inova, our research team is participating in clinical trials to explore new immunotherapy combinations for colon cancer and other GI cancers. Meanwhile, our cancer specialists draw on the most up-to-date research findings as we develop treatment plans for our patients.

To book an appointment with the specialists at the Inova Schar Cancer Institute, call 571-472-4724.