New findings from a clinical trial led by Memorial Sloan Kettering Cancer Center (MSK) reveal that immunotherapy alone can allow patients with mismatch repair-deficient (MMRd) cancers to avoid surgery, radiation, and chemotherapy, while maintaining their quality of life. The study, presented at the 2025 AACR Annual Meeting and published in The New England Journal of Medicine (NEJM), marks a potential paradigm shift in cancer treatment.
High Success Rates Across Multiple Cancers
The trial included 103 patients with stage 1-3 cancers, comprising 49 with rectal cancer and 54 with non-rectal cancers such as gastroesophageal, hepatobiliary, colon, genitourinary, and gynecologic tumors. Patients received Jemperli (dostarlimab), a PD-1 inhibitor developed by GSK, for six months.
Results were striking: 80% of patients responded to immunotherapy alone and did not require surgery, radiation, or chemotherapy. In particular:
- Rectal cancer patients: 100% complete response (49/49)
- Other cancers: 65% complete response (35/54)
- Total complete responses: 84, with 82 patients avoiding surgery
Preserving Quality of Life While Fighting Cancer
Dr. Andrea Cercek, gastrointestinal oncologist and co-director of the Center for Young Onset Colorectal and Gastrointestinal Cancer at MSK, emphasized, “This study shows that immunotherapy can replace surgery, radiation, and chemotherapy for MMRd solid tumors. Preserving a patient’s organs and quality of life, while effectively eliminating their cancer, is the best possible outcome. Patients can return to their daily routines and maintain independence.”
Dr. Luis Diaz Jr., Head of the Division of Solid Tumor Oncology at MSK, added, “The majority of patients saw their tumors completely disappear. Traditional treatments like surgery, chemotherapy, and radiation often affect quality of life, leading to infertility or bowel, bladder, and sexual dysfunction. These results could fundamentally change how we approach cancer care.”
Patient Perspectives Highlight Impact
Maureen Sideris, diagnosed with gastroesophageal junction cancer in 2022, shared her experience: “I was afraid surgery on my esophagus would prevent me from speaking for a while, which would have been awful. To have immunotherapy alone was just amazing.”
ctDNA Testing Enhances Early Response Detection
As reported by mskcc.org, the study also demonstrated the utility of ctDNA testing using Haystack MRD™, a tumor-informed liquid biopsy from Quest Diagnostics. It identified complete responses as early as 1.4 months, suggesting that ctDNA may become a key tool for assessing treatment response—particularly for tumors that are difficult to visualize or biopsy.
Building on Previous Successes
This phase 2 trial extends previous groundbreaking research in rectal cancer, where all patients treated with dostarlimab achieved a complete clinical response, with tumors disappearing entirely. The FDA granted dostarlimab Breakthrough Therapy Designation for rectal cancer treatment in December 2024.
Expanding Immunotherapy to More Cancer Types
For Drs. Cercek and Diaz, the next goal is to broaden this immunotherapy approach to additional cancer types. The trial demonstrates that immunotherapy not only offers a high rate of tumor response but also allows patients to avoid the side effects and organ loss associated with traditional cancer treatments, signaling a new era in precision oncology.