A groundbreaking clinical trial has demonstrated that every patient with a specific type of rectal cancer achieved complete remission using a single immunotherapy drug, potentially revolutionizing treatment for this challenging malignancy. The phase 2 study, conducted at Memorial Sloan Kettering Cancer Center, found that dostarlimab (Jemperli) eliminated cancer in all 14 patients with locally advanced rectal cancer harboring mismatch repair deficiency (MMRd) mutations.
Unprecedented Clinical Response
The trial results, published in the New England Journal of Medicine, represent what researchers believe may be the first time in cancer treatment history that 100% of patients in a clinical trial achieved complete remission. "I believe this is the first time this has happened in the history of cancer," said Dr. Luis Diaz Jr., senior author of the study and medical oncologist at Memorial Sloan Kettering Cancer Center.
Patients received dostarlimab, manufactured by GlaxoSmithKline, every three weeks for six months at approximately $11,000 per dose. The drug works by exposing cancer cells so the immune system can identify and destroy them, specifically targeting the "don't eat me" signal on cancer cells.
Targeting a Specific Genetic Subtype
The study focused exclusively on patients with MMRd mutations, found in approximately 5-10% of rectal cancer patients. These tumors typically respond poorly to conventional chemotherapy and radiation treatments, often requiring surgical removal with significant long-term consequences.
"When those mutations accumulate in the tumor, they stimulate the immune system, which attacks the mutation-ridden cancer cells," explained Dr. Diaz. "We thought, 'Let's try it before cancer metastasizes as a first line of treatment'."
Dr. David Agus, CBS News medical contributor, noted that "the treatment targets a subtype of rectal cancer that has the DNA repair system not working. When this system isn't working there are more errors in proteins and the immune system recognizes these and kills the cancer cells."
Avoiding Standard Treatment Complications
Traditional treatment for rectal cancer typically involves a combination of chemotherapy, radiation therapy, and surgery, which can result in life-altering side effects. "Surgery and radiation have permanent effects on fertility, sexual health, bowel and bladder function," said Dr. Andrea Cercek, the study's principal investigator and medical oncologist at Memorial Sloan Kettering.
"The implications for quality of life are substantial, especially in those where standard treatment would impact childbearing potential. As the incidence of rectal cancer is rising in young adults, this approach can have a major impact."
Patient Sascha Roth, the first participant enrolled in the trial, was preparing for weeks of radiation therapy when doctors delivered unexpected news. "Dr. Cercek told me a team of doctors examined my tests, and since they couldn't find any signs of cancer, Dr. Cercek said there was no reason to make me endure radiation therapy," Roth explained.
Safety Profile and Follow-up Results
After six months of treatment, all patients showed complete clinical response with no evidence of tumors detected through MRI scans, PET scans, endoscopy, and biopsy. Approximately three-quarters of patients experienced mild to moderate side effects, including rash, itching, fatigue, and nausea, but no serious adverse events were reported.
The median follow-up period reached one year, with some patients like Roth remaining cancer-free for two years. Follow-up periods for the 14 patients ranged from six to 25 months after trial completion, with no cancer recurrence observed in any participant.
Clinical Implications and Future Directions
Dr. Cercek emphasized the emotional impact of these results: "It's incredibly rewarding to get these happy tears and happy emails from the patients in this study who finish treatment and realize, 'Oh my God, I get to keep all my normal body functions that I feared I might lose to radiation or surgery.'"
The research team is investigating whether this immunotherapy approach could benefit patients with other MMRd tumors, including certain types of stomach, prostate, and pancreatic cancers.
Study Limitations and Expert Commentary
Dr. Hanna K. Sanoff from the University of North Carolina's Lineberger Comprehensive Cancer Center, who wrote an accompanying editorial, cautioned that questions remain about long-term outcomes. "Very little is known about the duration of time needed to find out whether a clinical complete response to dostarlimab equates to cure," Dr. Sanoff noted.
She emphasized that clinical complete response is not necessarily a surrogate for long-term cancer control, as cancer regrowth is generally expected in a minority of patients managed non-operatively. "Whether the results of this small study conducted at Memorial Sloan Kettering Cancer Center will be generalizable to a broader population of patients with rectal cancer is also not known."
The trial is expected to expand to approximately 30 patients total, which will provide a more comprehensive understanding of dostarlimab's safety and efficacy profile in this specific patient population. Despite the limitations, Dr. Sanoff acknowledged the significance of these findings: "These results are cause for great optimism."
The study represents what may be "an early glimpse of a revolutionary treatment shift," according to Dr. Sanoff, potentially offering eligible patients the possibility of cure without functional compromise.
