AACR 2025: PD-1 Inhibitor Dostarlimab Achieves Breakthrough in "Surgery-Free" Treatment of dMMR Tumors
Research Highlights
At the 2025 American Association for Cancer Research (AACR) Annual Meeting, Dr. Andrea Cercek from MSK Cancer Center reported a groundbreaking finding from a Phase II trial: PD-1 inhibitor dostarlimab monotherapy can achieve complete remission in patients with locally advanced dMMR tumors, avoiding the need for surgery. The study was simultaneously published in the *New England Journal of Medicine*.
Key Data
Patient Population
103 patients with stage II-III resectable dMMR tumors (49 rectal cancer, 54 non-rectal cancers, including gastroesophageal, hepatobiliary, genitourinary, and gynecological tumors)
Patients who achieved complete remission after 6 months of dostarlimab treatment were eligible for non-surgical treatment.
Efficacy Results
Rectal cancer group: 100% complete remission in 49 patients (data from 41 patients previously confirmed)
Non-rectal cancer group: 65% of patients (35/54) achieved complete remission
Of the 84 patients with complete remission, 82 chose non-surgical treatment.
Long-term Follow-up
92% of patients in the rectal cancer group were relapse-free for 2 years.
4 patients maintained remission for up to 5 years.
ctDNA Dynamic Monitoring
Patients with lower ctDNA levels during treatment were more likely to achieve complete remission.
Clinical Significance:
Organ Preservation: Avoids complex surgeries on the stomach, pancreas, and rectum, improving quality of life.
Potential Survival Benefit: Early-stage dMMR tumor patients may be able to skip traditional radiotherapy and chemotherapy.
Biomarker Application: ctDNA may become a tool for predicting treatment efficacy.
Expert Opinions
Dr. Cercek points out:
"This study demonstrates that patients with early-stage dMMR tumors may not need surgery or radiation therapy if they receive sufficient courses of immunotherapy. Especially for tumors affecting critical organs, organ preservation means a better quality of life."
Dr. Luis Diaz of MSK emphasizes:
"This finding opens up new avenues for neoadjuvant therapy and may be extended to non-dMMR tumors in the future."
Research Limitations and Future Directions
Current Limitations: Prostate and gastroesophageal tumors show weak responses; the influence of the tumor microenvironment needs further investigation.
Next Steps: Expand patient recruitment and explore combination therapy strategies.
Disclosure of Interests
This research was funded by Swim Across America, Stand Up To Cancer, and others. Dr. Cercek has consulted with several pharmaceutical companies and holds related patents.
Source: https://ascopost.com/news/april-2025/nonoperative-management-of-mismatch-repair-deficient-tumors/