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Small Cancer Trial Resulted In Complete Remission For All Participants

Source: Smithsonian Magazine, Margaret Osborne
Photo: Colon cancer cell illustration (KATERYNA KON/SCIENCE PHOTO LIBRARY via Getty Images)

The results are promising, but experts say the trial should be replicated

A very small trial of rectal cancer patients has produced unprecedented results: remission in 100 percent of its participants. The findings were published this week in The New England Journal of Medicine.

“I believe this is the first time this has happened in the history of cancer,” Luis A. Diaz Jr., an oncologist at Memorial Sloan Kettering Cancer Center and author on the new study, tells the New York Times’ Gina Kolata.

The trial was funded by the company GlaxoSmithKline, which developed a drug called dostarlimab, reports the Times. Patients in the trial took dostarlimab, an immunotherapy medicine that spurs patients’ immune systems to attack their cancers, every three weeks for six months.

All 12 participants had similar mutations in what’s called mismatch repair-deficient colorectal cancer, which occurs in about 5 to 10 percent of colorectal cancers, per the study. These tumors tend to respond poorly to standard chemotherapy.

“They lack a gene that enables them to repair their DNA and because of that, they have many, many mutations, and the immune system recognizes the cancer is foreign,” oncologist Andrea Cercek, a coauthor of the study from Memorial Sloan Kettering Cancer Center, tells CNN. “When we give immunotherapy, like dostarlimab, it really just revs up the immune system so that it sees the cancer and gets rid of it.”

Dostarlimab is an antibody that targets a protein called programmed cell death 1, or PD-1. PD-1 exists on the surface of T-cells produced by the immune system and helps the body recognize and destroy cancer cells. Cancer cells, in turn, can produce molecules that block PD-1 and evade detection by the immune system. Dostarlimab works by preventing this evasion by cancer cells, allowing the immune system to detect and decimate cancer cells.

The researchers had planned to follow up the dostarlimab treatment with standard chemoradiotherapy and surgery, but the patients didn’t need it. All 12 participants who completed the dostarlimab treatment and underwent 6 months of follow-up had no detectable cancer cells or significant side effects, per the study. Even up to 25 months later, no cases of progression or recurrence have been reported, per a statement.

Traditional colorectal treatments can have life-changing impacts, Hanna Sanoff of the University of North Carolina’s Lineberger Comprehensive Cancer Center, who wasn’t involved in the study but wrote an editorial about the research, tells NPR’s Sacha Pfeiffer and Jonaki Mehta.

“Surgery and radiation have permanent effects on fertility, sexual health, bowel and bladder function. The implications for quality of life are substantial, especially in those where standard treatment would impact childbearing potential,” Cercek says in the statement. “As the incidence of rectal cancer is rising in young adults, this approach can have a major impact.”

Experts caution that the trial was very small, and it’s too soon to know whether the patients will stay in remission. Even patients with a complete response to radiation and chemotherapy can see cancer regrowth—about 20 to 30 percent of patients when the cancer is managed nonoperatively, writes Sanoff in the editorial.

PD-1 takes part in a broader biological process called “checkpoint inhibition,” a sort of on/off switch for immune cells. Targeting PD-1 and other parts of checkpoint inhibition for cancer treatment is currently one of the most active areas of research in oncology.

“These results are cause for great optimism, but such an approach cannot yet supplant our current curative treatment approach,” Sanoff writes, adding that the trial should be replicated.

“What I’d really like us to do is get a bigger trial where this drug is used in a much more diverse setting to understand what the real, true response rate is going to be,” she tells NPR. “It’s not going to end up being 100 percent. I hope I bite my tongue on that in the future, but I can’t imagine it will be 100 percent. And so when we see what the true response rate is, that’s when I think we can really do this all the time.”

Margaret Osborne is a freelance journalist based in the southwestern U.S. Her work has appeared in the Sag Harbor Express and has aired on WSHU Public Radio.

https://www.smithsonianmag.com/smart-news/small-cancer-trial-resulted-in-complete-remission-for-all-participants