Immunotherapy Alone Achieves Complete Response in Mismatch Repair-Deficient Gastroesophageal Junction Cancer, Sparing Patient from Chemotherapy and Surgery
核心洞察
A 74-year-old patient with locally advanced gastroesophageal junction cancer (搜索) achieved no evidence of disease after three months of ipilimumab and nivolumab immunotherapy alone, avoiding chemotherapy and total stomach removal.
The tumor was found to harbor mismatch repair deficiency (搜索) (dMMR), a biomarker that makes certain gastric cancers highly responsive to immunotherapy, as demonstrated in a recent French study showing ~60% complete response rates.
CU Anschutz oncologist Sunnie Kim, MD, now tests all patients with localized stomach and esophageal cancer for dMMR, offering a non-chemotherapy regimen to eligible patients.
When Don McCoy, 74, was diagnosed with gastroesophageal junction cancer (搜索) in 2025, his local oncologists recommended an aggressive treatment plan: chemotherapy to shrink the tumor, followed by total stomach removal — a life-altering surgery. McCoy refused. "At the end of that conversation, I said 'No, sorry, you guys. I really appreciate what we're doing so far, but I want a second opinion,'" he recalled.
That decision led him to the University of Colorado Anschutz Cancer Center (搜索), where Sunnie Kim, MD, associate professor of medical oncology, identified a critical biomarker that would change everything: his tumor harbored mismatch repair deficiency (搜索) (dMMR), a cellular defect that renders certain cancers exquisitely sensitive to immunotherapy.
A Biomarker-Driven Paradigm Shift
"In most situations with locally advanced gastric cancer, we recommend aggressive chemotherapy with immunotherapy, and it's a pretty hefty regimen for patients," said Kim. "In Don's case, the surgery would have been a total stomach removal, which is a life-altering surgery that would require him to change his eating habits completely."
Kim drew on findings from a recent small but pivotal study conducted in France, where patients with early-stage stomach cancers expressing mismatch repair deficiency (搜索) received a combination of two immunotherapy drugs without chemotherapy prior to surgery. When surgery was eventually performed, approximately 60% of patients had no disease remaining in the primary organ.
"As a field, we've been talking about whether these patients even need surgery. They may be cured with immunotherapy alone," Kim said.
Treatment Course and Outcome
McCoy began a 12-week, six-treatment course of immunotherapy infusions with ipilimumab and nivolumab in August 2025. True to Kim's prediction, he experienced no hair loss and ultimately avoided surgery entirely.
After three months, scans showed little to no cancer. A follow-up endoscopy revealed a potentially concerning ulceration, but biopsy results came back negative for cancer cells. During this period, McCoy developed liver enzyme abnormalities — a known side effect of immunotherapy — prompting a pause in treatment while Kim prescribed steroids.
Subsequent scans showed further improvement. The ulceration appeared smaller on endoscopy, biopsy remained negative, and circulating tumor DNA (ctDNA) testing of the blood also returned negative for cancer cells. McCoy is now off immunotherapy and on a surveillance plan.
"We're hopeful that he is going to be cured with immunotherapy alone," Kim said.
Implications for Clinical Practice
Kim now tests all patients diagnosed with localized stomach and esophageal cancer for mismatch repair deficiency (搜索), aiming to identify those who might benefit from a chemotherapy-free approach. "To do it without chemotherapy means the patients don't need a port. It's a little thing, but all those little things add up to improving patients' quality of life as they go through therapy," she said. "It's been nice to be able to offer a subset of these patients with a non-chemo regimen and have it be this effective."
For McCoy, who with his wife owns several retail stores in Colorado ski areas, avoiding chemotherapy side effects and surgical recovery meant he could continue working and pursuing hobbies including golfing, skiing, and racing his Corvette.
"I'm really glad to be on the cutting edge of something, and I didn't have to get cut," McCoy said. He emphasized a principle he has long followed: "I don't care what it is, but don't settle on the first thing. Get a second opinion, and I recommend that to anybody. If I would have done the chemo and the surgery, I could be sitting here a shell of myself — or not be sitting here at all."