A clinical trial led by Memorial Sloan Kettering Cancer Center (MSK) has delivered promising results that could revolutionize cancer treatment. Spearheaded by gastrointestinal oncologists Dr. Andrea Cercek and Dr. Luis Diaz Jr., the Phase 2 trial demonstrated that immunotherapy alone can effectively treat mismatch repair-deficient (MMRd) cancers, allowing patients to avoid surgery, radiation, and chemotherapy.
The findings were presented at the American Association for Cancer Research (AACR) Annual Meeting 2025 and simultaneously published in the New England Journal of Medicine.
80% of Patients Avoided Surgery and Traditional Therapies
In the trial, 80% of patients achieved a complete clinical response after six months of treatment with dostarlimab (Jemperli), a PD-1 checkpoint inhibitor developed by GSK. These patients did not require surgery, chemotherapy, or radiation, marking a significant shift in treatment for cancers with the MMRd genetic mutation.
“This study shows that immunotherapy can replace surgery, radiation, and chemotherapy for mismatch repair-deficient solid tumors,” said Dr. Cercek. “This helps patients preserve their organs and avoid the harsh side effects typically associated with traditional cancer treatments.”
Expanded Study Builds on Landmark Rectal Cancer Trial
As reported by medicalxpress, this trial builds on earlier groundbreaking research, where all patients with rectal cancer treated with dostarlimab experienced tumor disappearance. In December 2024, the U.S. FDA granted Breakthrough Therapy Designation to dostarlimab for MMRd rectal cancer based on those results.
The current study enrolled 103 patients with stage 1–3 cancers, including:
- 49 patients with rectal cancer
- 54 patients with non-rectal cancers (gastroesophageal, hepatobiliary, colon, genitourinary, and gynecologic cancers)
All participants received dostarlimab for six months. The treatment enabled most patients to avoid surgery and the complications that come with it.
Improving Quality of Life Through Organ Preservation
Patients who responded well to the immunotherapy were able to preserve their organs and maintain a high quality of life. This is especially important in cases like rectal cancer, where surgery and radiation often lead to infertility and impair bowel, bladder, or sexual function.
Dr. Diaz emphasized the impact:
“The majority of patients in the trial saw their tumors completely disappear. These results could change how we treat some cancers. Current treatments like surgery and radiation can have long-term effects on patients’ daily lives.”
A Patient’s Perspective: Avoiding Invasive Surgery
Maureen Sideris, diagnosed with gastroesophageal junction cancer in 2022, shared her experience:
“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. To have immunotherapy alone was just amazing.”
Her story underscores the personal benefits of avoiding surgical procedures that could drastically alter daily living.
ctDNA Testing Proves Effective for Monitoring Response
The trial also incorporated circulating tumor DNA (ctDNA) testing using Haystack MRD, a tumor-informed liquid biopsy from Quest Diagnostics. Researchers found that ctDNA identified complete response as early as 1.4 months into treatment.
These findings suggest that ctDNA could become a valuable tool for real-time response assessment, particularly for tumors located in hard-to-biopsy or visualize regions. It could enhance clinical decision-making in the neoadjuvant setting as immunotherapy moves further upstream in treatment timelines.
Looking Ahead: Expanding the Approach
Drs. Cercek and Diaz now aim to expand this immunotherapy-first strategy to a broader range of cancers with MMRd mutations. Their goal is to continue replacing invasive, toxic therapies with effective and organ-preserving alternatives.
“This approach is about more than just treating cancer,” said Dr. Cercek. “It’s about preserving quality of life and helping people return to their lives with as few limitations as possible.”