Benefits of Immunotherapy for Esophageal Cancer
- Two immunotherapy drugs are approved for esophageal cancer — Opdivo and Keytruda.
- Keytruda is only approved for people who test positive for a protein called PD-L1 and who have tried at least one treatment before.
- Opdivo doesn’t require a positive PD-L1 test.
- Keytruda is only used when other treatments fail, but it’s now being investigated as a first-line therapy.
- Immunotherapy doesn’t cause nausea, hair loss, and numbness and tingling like chemotherapy.
“Immunotherapies are being tested not only in metastatic patients, but also in earlier settings combined with chemotherapy,” Dr. Rutika Mehta, medical oncologist at Moffitt Cancer Center in Tampa, FL, tells SurvivorNet. “These immunotherapies have a survival benefit.”Read More
Esophageal cancer isn’t as common as breast or prostate cancer, but it tends to have a worse prognosis. Five-year survival rates after diagnosis are just under 20 percent. Typically people will get surgery and a combination of chemotherapy and radiation (collectively termed “chemoradiation”), but often the cancer comes back after these treatments. The recent introduction of immunotherapy has offered hope to people whose cancer continues to grow after treatment.
How Immunotherapy Works Against Esophageal Cancer
Normally the immune system finds and destroys cancer cells, just as it does bacteria, viruses, and other threats. But when cancers invade the body, they have a sneaky way of preventing the immune system from finding them—they block certain receptors on immune cells.
Head & neck surgeon Dr. Scott Strome explains immunotherapy in Star Trek terms
“Immunotherapy helps to reset that balance,” Dr. Mehta says. “It helps to unblock the receptors on immune cells that the cancer cells are blocking.” Essentially, this “resets” the immune cells so they can fight the cancer.
Some esophageal cancers respond better to immunotherapy than others. Squamous cell cancers are more responsive to this treatment because they already contain a lot of immune cells to activate. These are the so-called “hot tumors.”
Immunotherapy doesn’t work as well against adenocarcinomas, which make up the majority of esophageal cancers, because they’re lower in immune cells. These are known as “cold tumors.” “They need special effort to get the immune system activated to kill cancer cells,” Dr. Mehta says.
Keytruda: First in Its Class
The breakthrough in immunotherapy for esophageal cancer came in 2019, when Keytruda became the first of these drugs to earn FDA approval. Keytruda treats locally advanced (meaning it has spread into nearby tissues) or metastatic (meaning it has spread to distant organs) squamous cell esophageal cancer. This treatment is also approved to treat melanoma, as well as for lung cancer, colon cancer, and head and neck cancers, among others.
Keytruda has been an exciting advancement, but it’s not right for everyone with esophageal cancer. To be eligible for this drug, you also have to test positive for PD-L1, a protein that helps stop your immune cells from attacking normal cells. If you have a lot of PD-L1, it’s easier for the cancer to hide from your immune system. Between 40% and 50% of people with esophageal cancer have this protein, Dr. Mehta says. Keytruda works by blocking PD-L1, which unleashes your immune system to go after the cancer.
Another requirement is that you’ve already tried at least one treatment, making Keytruda a second-line therapy in this instance.
In March 2021, Keytruda received FDA approval in combination with platinum and fluoropyrimidine-based chemotherapy for patients with metastatic or locally advanced esophageal or gastroesophageal (GEJ) (tumors with epicenter 1 to 5 centimeters above the gastroesophageal junction) carcinoma. This is a first line therapy available for patients who are not candidates for surgery or radiation.
Opdivo: New Immunotherapy Kid on the Block
Keytruda was the only immunotherapy drug on the esophageal cancer scene until June 2020, when the FDA approved Opdivo. This treatment also has FDA approval for melanoma, lung cancer, colorectal cancer and a few other cancer types.
Opdivo has one notable advantage over Keytruda. “You don’t need to test the tumor’s PD-L1 score,” says Dr. Mehta. “All patients with squamous cell esophageal cancers can get it.”
Opdivo is approved for advanced squamous cell esophageal cancers, regardless of their PD-L1 status. Its manufacturer, Bristol Myers Squibb, also had good news from a recent phase III study. Researchers found that people who received Opdivo after surgery and chemoradiation had better disease-free survival (the amount of time when their scans showed no signs of cancer) compared to people who got a placebo.
These immunotherapy drugs have improved not only the length, but also the quality of life for people with esophageal cancer who’ve taken them. “The powerful part of immunotherapy is that it does not create the same side effects as chemotherapy,” Dr. Mehta says. That means people who take immunotherapy can avoid the hair loss, nausea and vomiting, and numbness and tingling that chemotherapy often causes.
Yet immunotherapy isn’t risk-free. “When the immune system is revved up and killing cancer cells, it can also attack the normal organs of the body — lungs, heart, liver, kidneys, bowel, spinal cord,” Dr. Mehta says. Although these types of side effects are uncommon, they can be serious and require medical care when they do happen.
The side effects of immunotherapy aren’t forever, says oncologist Dr. Anna Pavlick
People who start on immunotherapy will also need to be patient. These drugs take time to work. It can take about 12 weeks to see signs that the tumor is shrinking on scans, Dr. Mehta says.
She adds that not everybody who gets immunotherapy responds to it. “But if you do respond to immunotherapy, some of these responses can be durable. They can prolong survival.”
The MSI-High Advantage
The improvement in survival is even bigger for people with MSI-high tumors. MSI-high stands for microsatellite instability-high. It’s when cells have so many DNA defects that it’s hard for them to repair themselves, and they’re more likely to turn into cancer. That same feature makes the cancer cells look so abnormal that they’re easier for the immune system to find, which makes them a better target for immunotherapy.
Less than 5% of the people with esophageal cancer that Dr. Mehta sees have MSI-high tumors, “but these are patients who derive significant benefit from immunotherapy,” she says. In studies, 50% to 60% of patients with these tumors shrank with Keytruda. “These are ginormous responses…but these are just a minority of patients.”
Is Immunotherapy Right for You?
Keytruda and Opdivo are showing great promise in people with esophageal cancer. They’re not for everyone, but if you’re diagnosed, it’s worth getting tested to learn your PD-L1 and MSI-high status and find out if you’re a candidate. “It’s important for a patient to be aware of immunotherapy as a treatment option,” Dr. Mehta says. “I highly encourage patients to ask their physicians about immunotherapy.”