Background
Prospective single-arm phase II trial (n=12) of neoadjuvant dostarlimab in mismatch repair-deficient (dMMR) stage II–III rectal adenocarcinoma. Chemoradiotherapy and surgery were planned only for patients with persistent disease.
Interventions and follow up
Regimen: dostarlimab 500 mg IV every 3 weeks for 9 cycles (6 months) as neoadjuvant therapy
Subsequent therapy: chemoradiotherapy ± surgery reserved only for persistent/residual disease
Primary endpoint: sustained clinical complete response at 12 months and/or pathologic complete response, plus overall response
Median follow up: 6.8 months at initial report
Subsequent therapy: chemoradiotherapy ± surgery reserved only for persistent/residual disease
Primary endpoint: sustained clinical complete response at 12 months and/or pathologic complete response, plus overall response
Median follow up: 6.8 months at initial report
Results
Clinical complete response: 100% (12/12 patients)
Need for chemoradiotherapy or surgery: none required
Durability: responses sustained on follow-up; rectal mass FDG uptake and clinical symptoms resolved
Need for chemoradiotherapy or surgery: none required
Durability: responses sustained on follow-up; rectal mass FDG uptake and clinical symptoms resolved
Adverse events
Grade 3–4: none reported
Dermatologic/constitutional: rash 31%, pruritus 25%, fatigue 25%
Other low-grade: nausea 19%, fever 13%, diarrhea 13%, dry eye 13%
Dermatologic/constitutional: rash 31%, pruritus 25%, fatigue 25%
Other low-grade: nausea 19%, fever 13%, diarrhea 13%, dry eye 13%
Conclusions
Mismatch repair-deficient locally advanced rectal cancer is highly sensitive to single-agent PD-1 blockade with dostarlimab, with all patients achieving clinical complete response and avoiding chemoradiotherapy and surgery, with minimal toxicity.
Key Limitations
Very small single-arm cohort (n=12), single center, short follow-up at initial report. Long-term durability of organ preservation and generalizability remain to be confirmed in larger studies.
Clinical Context
Landmark proof-of-concept for non-operative management of dMMR rectal cancer with PD-1 blockade. Supports MMR/MSI testing of all rectal cancers and informs ASCO/ESMO discussion of immunotherapy-based organ preservation; broader confirmatory trials ongoing.