A New Approach to MMRd/MSI-H Tumors
At the AACR Annual Meeting 2025 in Chicago, Dr. Andrea Cercek presented compelling data on PD-1 immunotherapy for MMRd/MSI-H tumors. Her phase II trial of 117 patients showed a 92% recurrence-free survival (RFS) rate at two years, with 35% experiencing no adverse events. This study, focusing on cancers like colorectal and endometrial, suggests PD-1 immunotherapy could redefine treatment for MMRd/MSI-H tumors. Watch our detailed video below for more insights from AACR 2025.
What Are MMRd/MSI-H Tumors?
MMRd/MSI-H tumors have defects in DNA mismatch repair, leading to high mutation loads. This makes them more responsive to PD-1 inhibitors like dostarlimab, which help the immune system target cancer cells. Dr. Cercek’s prior rectal cancer study, where all 42 patients achieved remission, set the stage for this broader research, earning dostarlimab FDA fast-track approval for MMRd/MSI-H cancers.
Key Findings from AACR 2025
The study revealed impressive outcomes across various MMRd/MSI-H tumors:
- Colorectal cancer achieved a 100% complete clinical response.
- Non-rectal cancers, such as endometrial and gastric, had a 65% complete response rate.
- Of 84 patients with complete responses, 82 avoided surgery, highlighting organ preservation potential.
- Lower ctDNA levels during therapy predicted better tumor clearance, offering a potential biomarker.
However, pancreatic cancer showed weaker results, with only 10% achieving a complete response due to its immunosuppressive tumor microenvironment.
Implications for Cancer Management
PD-1 immunotherapy for MMRd/MSI-H tumors offers a non-operative option, especially for colorectal cancer. It preserves organs and improves quality of life, but challenges remain for cancers like gastroesophageal and pancreatic. Future research will explore the tumor microenvironment to enhance outcomes in these less responsive cases.
Why This Matters for Oncology
For oncology professionals, these findings underscore the potential of PD-1 immunotherapy in MMRd/MSI-H tumors. The high RFS rate and minimal adverse events make it a promising option, while the use of ctDNA as a biomarker could guide personalized treatment. Patients benefit from less invasive approaches, maintaining their quality of life.
Watch the Full Video for More Insights
Our video breaks down the AACR 2025 presentation, including expert commentary on the future of PD-1 immunotherapy for MMRd/MSI-H tumors. Learn how this research could impact cancer care and what challenges lie ahead.
Related Links:
https://www.nejm.org/doi/full/10.1056/NEJMoa2404512