- A new clinical trial shows the immunotherapy drug dostarlimab could eliminate the need for surgery and chemotherapy in certain cancers.
- The results are a medical breakthrough since the drug could help preserve organs.
- People with the dMMR gene mutation, which most often presents in colorectal cancer, are the best candidates for this novel treatment.
New findings from a clinical trial highlight the potential for neoadjuvant immunotherapy to eliminate the need for surgery in patients with a particular type of cancer, helping them maintain a higher quality of life.
“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,” lead author Andrea Cercek, MD, a gastrointestinal oncologist and co-director of the Center for Young Onset Colorectal and Gastrointestinal Cancer at Memorial Sloan Kettering Cancer Center, said in a press release.
“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,” Cercek continued.
This phase 2 study builds on previous landmark research, in which colorectal cancer patients receiving the immunotherapy drug dostarlimab experienced complete tumor remission.
The goal of the researchers was to see if the immunotherapy drug dostarlimab could help people with mismatch repair–deficient (dMMR) cancers avoid surgery, radiation, and chemotherapy.
The National Cancer Institute (NCI) states that
The study analysis included 117 patients with early stage solid tumors exhibiting dMMR.
These individuals were given nine doses of dostarlimab (one dose every three weeks) for six months.
After treatment ended, the researchers checked to see if the cancer was gone.
Out of 103 patients who completed treatment, 82% had no signs of cancer, and 80% were deemed to be able to skip further treatment such as surgery, chemotherapy, and radiation.
Additionally, among those who had colorectal cancer, all 49 had a complete response to treatment, allowing them to avoid surgery.
The researchers further found that the results were long-lasting, with 92% of patients still being cancer-free after two years.
For the most part, the side effects of dostarlimab were mild and included symptoms such as fatigue or rash.
The authors noted that the drug worked quickly; in many patients, the cancer was no longer visible on scans by around six months. Blood tests for tumor DNA were negative in most people within 1 to 2 months.
Steven Quay, MD, PhD, a physician-scientist specializing in cancer research and the founder of Atossa Therapeutics, described this study as “nothing short of a paradigm-shifter.” Quay wasn’t involved in the clinical trial.
“It shows that neoadjuvant immunotherapy (specifically PD-1 blockade with dostarlimab) can eliminate the need for surgery in a substantial proportion of patients with mismatch repair–deficient (dMMR) tumors,” he told Healthline.
Quay further noted that this doesn’t just mean engaging in watchful waiting when tumors are small and may never progress to the point of causing the patient harm.
“[W]e’re talking about avoiding curative-intent surgery altogether,” he said.
Quay further explained that these findings challenge two long-standing assumptions: that curing solid tumors requires surgical removal, and that immunotherapy is only effective for cancers that have spread or cannot be surgically removed.
If these results are confirmed in future studies, Quay says some cancers might one day be treated entirely without surgery, marking a shift in cancer care from cutting tumors out to harnessing the immune system to eliminate them.
“It’s equivalent to going from ‘cutting out the fire’ to ‘training the firefighters,’” he explained.
Pashtoon Kasi, MD, MS, the medical director of gastrointestinal medical oncology at City of Hope Orange County in Irvine, California, said drugs like dostarlimab rely on your body’s own cancer-fighting ability. Kasi wasn’t involved in the clinical trial.
“Simplistically, these drugs are called immunotherapy and take the brakes off your own immune or defense system,” he said, adding that we probably develop several cancers during our lifetime. However, our body usually can get rid of them.
“Sometimes though the cancer hides under the immune system radar, or the defenses are down, and that cancer gets a free pass to develop and spread,” Kasi told Healthline.
Delving more deeply into the mechanisms, Quay explained that dostarlimab is a PD-1 immune checkpoint inhibitor.
Using the metaphor of the immune system as a sniper unit, he said: “Tumors hijack the PD-1 pathway to tell immune cells, ‘Don’t kill me — I’m friendly!’”
However, dostarlimab blocks PD-1, which once again allows the body’s T-cells to recognize and attack the tumor.
“The key here is not where the tumor is,” said Quay, “but what it’s made of genetically. Patients who stand to benefit most are those with mismatch repair–deficient (dMMR) tumors.”
According to Quay, these tumors are “juicy targets” for immune checkpoint blockade due to the many foreign proteins found on the tumor’s surface.
Specifically, the cancers included in this study were colorectal cancer and other non-rectal solid tumors, including gastrointestinal, gynecologic, and genitourinary cancers.
Kasi added that he advises all of his patients to be tested for dMMR.
“If anyone’s cancer is mismatch repair deficient (dMMR), while chemotherapy does not work well, immunotherapy on the other hand works very well,” he said.
The bottom line? “If you’re a patient with a dMMR tumor, no matter if it’s in the colon, uterus, pancreas, or stomach, you’re potentially in the immunotherapy winner’s circle,” concluded Quay.
