Breakthrough for People Facing Gastric and Esophageal Cancer

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Cecilia Defoe and Wade Quattlebaum were both diagnosed with advanced cancer involving the esophagus that metastasized (spread). Both were told their outlook looked grim.

And both came to Memorial Sloan Kettering to take part in separate clinical trials led by Yelena Janjigian, a physician-scientist and Chief of the Gastrointestinal Oncology Service.

Today, Cecilia and Wade have returned to their lives and the things they love.

And the two therapies they were given both got the green light by the FDA as a result of Dr. Janjigian’s work, offering important new options to all people with cancer of the esophagus and stomach cancer, also called gastric cancer.

From Heartburn to Cancer

Wade Quattlebaum was surprised when heartburn flared in his early 30s. “I never had heartburn in my life,” he says. “But I figured it was just part of getting older.”

After months of taking over-the-counter medications, Wade saw a doctor in his hometown of Albany, Georgia. He had moved back there several years earlier, explaining, “I came home to help take care of my sister when she got brain cancer. There’s a lot of cancer in my family.”

The news about his own health turned out to be frightening. “I was diagnosed with a cancerous tumor at the bottom of my esophagus and was told the cancer had spread. The local oncologist said he couldn’t do anything for me.”

Specialists at a much larger hospital also told Wade they couldn’t help. “They told me I was too far along and that I should go home to be comfortable and finish out my life.” He continues, “I had seen my sister and father go through pretty extensive chemotherapy. I didn’t want that. I planned to enjoy the time I had left.”

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HER2-Positive Esophageal Cancer

That’s when family friends who work in the medical field stepped in. They researched clinical trials in which new therapies are investigated.

Wade went first to a leading cancer center where he learned his cancer was HER2-positive. HER2 is a gene that can produce too much of a protein that fuels cancer growth. About one out of five people with esophageal and stomach cancer have HER2-positive tumors, and the gene can also play a role in many other cancers, including breast cancer.

Eventually, Wade learned of a clinical trial led by MSK researchers aimed at cancers like his. He and his mother came to New York City from Georgia to meet with the trial’s principal investigator, Dr. Janjigian. “I liked her immediately,” says Wade. “She didn’t really sugar coat anything, and that fits my personality. We signed up for the trial that first day.”

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Adding Immunotherapy

Yelena Y. Janjigian, medical oncologist

Yelena Y. Janjigian, Chief, Gastrointestinal Oncology Service

Dr. Janjigian explains that the trial is “for patients who have not received any sort of treatment and are newly diagnosed with metastatic cancer. They have advanced disease where surgery is not possible.”

The goal of the study was to see if the standard treatment for Wade’s type of cancer could be improved by adding a form of immunotherapy, which uses the patient’s own immune system as an ally against cancer. 

Dr. Janjigian explains that “the typical treatment for cancer like Wade’s is chemotherapy and trastuzumab (Herceptin®). It’s a targeted therapy that binds to a switch on the cancer cell that affects HER2. The drug turns off the switch so HER2 doesn’t fuel cancer growth anymore.”

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How Checkpoint Inhibitors Fight Cancer

The problem, however, “is that trastuzumab cures very few people, and after several months, cancer usually recurs,” says Dr. Janjigian.

Her clinical trial added a new player to the mix — the immunotherapy treatment pembrolizumab (Keytruda®).

Pembrolizumab is a kind of immunotherapy known as a checkpoint inhibitor. A checkpoint is like a built-in brake on powerful immune cells to keep them from attacking healthy cells.

Cancer cells can sometimes fool immune cells with an invisibility shield to avoid detection. The checkpoint inhibitor overcomes the cancer cell’s trick, which frees immune cells to recognize and attack cancer cells. The goal, says Dr. Janjigian, “is to do a copy and paste of powerful immune system T cells that recognize the cancer and know how to fight it so lots of them can go after the cancer cells.”

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New Hope

At the start of the trial, Wade says, “I didn’t expect much. Many of my family members have died from cancer. I knew statistically that my chances of survival were not good.”

But three weeks after his first dose of pembrolizumab and trastuzumab, Wade found new hope. “They did a scan, and my cancer had decreased more than 40%. It was a massive decrease.” A second and third dose of combined treatment reduced his cancer even further.

Some changes to Wade’s treatment regimen were needed to deal with side effects, and he also credits a change in his diet with helping his health. He says, “Now, I have clean scans. I went from stage IV, with cancer everywhere from my neck to my pelvis, to clean scans in two and a half years. Good grief!”

Today, Wade is back in the swing of it in Georgia, “working 12-hour days” selling agricultural products like seeds and pesticides to farmers, and hunting and fishing in his spare time.

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‘Most Satisfying Moments of My Career’

Dr. Janjigian cautions that not all people on this therapy can expect the same response as Wade.

However, one of the standout data points from the trial is how many people with HER2-positive esophageal and gastric cancers are helped by adding pembrolizumab to standard care. Dr. Janjigian explains: “Typically for treatments with trastuzumab, you would expect about half of people to respond, meaning their cancer would shrink by 30%.”

However, with pembrolizumab teaming up with trastuzumab, she says, “Nine out of 10 people saw their cancer shrink dramatically, and about one out of every five people had cancer disappear with clean scans. That was never seen before.” She continues, “Being able to tell people with stage IV cancer that I now can’t see any signs of cancer is probably one of the most satisfying moments in my career.”

Because of the trial led by Dr. Janjigian, the FDA gave accelerated approval to the therapy in May 2021, adding gastric and gastroesophageal cancers to the growing list of malignancies for which immunotherapy can help.

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HER2-Negative Gastric and Esophageal Cancer

Most esophageal and gastric cancers are HER2-negative, affecting four out of every five patients. Dr. Janjigian led a large clinical study to help those people as well.

Cecilia Defoe taught high school science and biology in Brooklyn public schools for 15 years. In 2014, she says, “I started feeling different. Eventually, it got so bad my husband and teenage daughter had to help me up the stairs.”

Doctors couldn’t find the cause. One night, Cecilia found it so hard to breathe and swallow she was forced to go to the emergency room. Scans showed a tumor blocking her esophagus. She was diagnosed with stage III gastroesophageal (where the esophagus and stomach connect) cancer and underwent chemotherapy and radiation at a hospital in Brooklyn, but her cancer continued to grow.

Immunotherapy at MSK
Cancer is smart, but your immune system is smarter. Discover how Memorial Sloan Kettering is deploying immunotherapy to fight cancer.
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‘I Could Tell It Was Shrinking’

One of her oncologists thought Cecilia might be helped by a clinical trial. She found just what she was hoping for nearby in Manhattan at MSK. The trial being led by Dr. Janjigian was aimed at bringing new treatments to HER2-negative cancers like Cecilia’s.

The trial was investigating whether people were helped when immunotherapy was added to the standard of care. In the trial Cecilia joined, the immunotherapy was again a checkpoint inhibitor very similar to pembrolizumab, but this time it was nivolumab (Opdivo®). It was added to the standard chemotherapy regimen.

Within weeks, Cecilia reported improvement. “When I started the trial, one lymph node was so swollen I couldn’t lie down on my right side. But I was elated to tell Dr. Janjigian that I could feel it was shrinking and breaking apart.” Eventually, the new therapy shrank all the metastases.

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FDA Approval

Cecilia’s course of treatment had many ups and downs. But today she and her family have picked up where they left off.

She credits her strong faith, a positive mental outlook, and her confidence that the clinical trial would advance the understanding of cancer. “I went into the trial knowing that even if it didn’t work for me, but did benefit someone else, then I’m happy. I will have done what I set out to do.”

In the end, the clinical trial not only helped Cecilia, who has been in remission since 2017, but also led to an FDA approval for the therapy.

The FDA said the treatment “is the first in more than a decade to show survival benefit for people with advanced or metastatic gastric cancer who are being treated for the first time.”

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Inspiration at Home

Cecilia’s experience also changed lives closer to home.

She explains, “My daughter Anelisa has been part of my cancer experience since she was a teenager. She saw the care and attention that was given to me and how well it worked. She became a physical therapy aide and is now applying to schools to become a Physician Assistant. I’m very proud.”

 
Key Takeaways
  • The FDA has granted accelerated authorization to a therapy involving pembrolizumab (Keytruda®) for people with gastric cancer that is HER2-positive.
  • The FDA has granted approval to a therapy involving nivolumab (Opdivo®) for people with gastric cancer that is HER2-negative.
  • MSK’s Yelena Janjigian led the clinical trials that resulted in these FDA approvals.
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Dr. Janjigian has received research funding from the National Cancer Institute (NCI), Cycle for Survival, Fred’s Team, Rgenix, Bayer, Genentech/Roche, Bristol Myers Squibb, Eli Lilly, Merck, and the US Department of Defense. Dr. Janjigian has received consulting or advisory board fees from Bristol Myers Squibb, Merck Serono, Merck, Eli Lilly, Daiichi-Sankyo, Pfizer, Bayer, Imugene, AstraZeneca, Zymeworks Inc., Seattle Genetics, and Basilea Pharmaceutica. She has received speaker’s bureau fees from the American Society of Clinical Oncology. She has also received stock options and consulting fees from Rgenix.