Results from a groundbreaking clinical trial could soon change the way certain types of cancers are treated. A study published Sunday in the New England Journal of Medicine found that immunotherapy could replace surgery for patients with locally advanced mismatch repair-deficient (MMRd) solid tumors — which would preserve their quality of life.
What is immunotherapy for cancer?
According to the American Cancer Society, immunotherapy is a type of cancer treatment in which a patient’s own immune system is boosted or changed to fight cancer cells. Sometimes, it can work by stimulating someone’s natural defenses to make them stronger and more effective at finding and attacking cancer. Other times, it can involve using lab-m substances that act like components of the immune system — like the proteins monoclonal antibodies, which bind to targets on cancer cells so the immune system can identify them better and destroy them.
What did the study find?
The phase 2 study was conducted by gastrointestinal oncologists Andrea Cercek, MD, and Luis Diaz Jr., MD and led by Memorial Sloan Kettering Cancer Center and funded substantially by Swim Across America and Stand Up to Cancer. It was an extension of game-changing research from MSK that came out in December 2024, which saw rectal cancer disappear in 100 percent of patients who took dostarlimab (also known as Jemperli), a form of immunotherapy, in the small trial. 42 people completed the treatment and showed no signs of having cancer afterwards. Because of the success of the treatment, the FDA granted dostarlimab a “Breakthrough Therapy Designation” for treating people with MMRd rectal cancers.
The follow-up trial included 103 patients with stage 1-3 cancer. 49 patients had rectal cancer and 54 had non-rectal cancers, including gastroesophageal, hepatobiliary, colon, genitourinary, and gynecologic. They all had MMRd cancer, which means the cells have mutations in the genes that help correct mistakes when DNA is copied — and if a cell cannot fix the mistakes, it becomes cancerous. According to the National Cancer Institute, MMRd cancer is most common in colorectal cancer. The usual course of treatment for MMRd cancers is surgery, radiation, and chemotherapy. The study set out to examine whether just treating patients with immunotherapy for six months would be effective at treating cancer.
In the study, 100 percent of the patients with rectal cancer had a clinical complete response (meaning all signs of cancer had disappeared) and 65 percent of those with other types of cancer saw their tumors disappear. In total, about 80 percent of patients who were treated with immunotherapy did not have to undergo surgery.
“This study shows that immunotherapy can replace surgery, radiation, and chemotherapy for mismatch repair-deficient solid tumors, which could help patients preserve their organs and avoid the harsh side effects of chemo and radiation,” said Dr. Andrea Cercek, gastrointestinal oncologist and co-director of the Center for Young Onset Colorectal and Gastrointestinal Cancer at MSK.
“Preserving a patient’s quality of life while also successfully achieving positive results in eliminating their cancer is the best possible outcome. They can return to their daily routines and maintain their independence.”
Maureen Sideris, a participant in the trial who was diagnosed with gastroesophageal junction cancer in 2022, said, “I was afraid that if I got surgery on my esophagus, I wouldn’t be able to talk for a while, which would be awful.” Sideris did not have to undergo surgery thanks to the success of the immunotherapy alone, which she said, “was just amazing.”
Dr. Cercek and Dr. Diaz now hope to be able to use this approach to treat even more types of cancer.
