A Systematic Review on Dostarlimab-gxlyin in the Treatment of Rectal Cancer: Efficacy, Safety, and Future Directions

Abstract Dostarlimab-gxly, a monoclonal anti–PD-1 antibody, has been recognized as being effective for rectal cancer in patients whose tumors are mismatch repair deficient. Even though promising preliminary clinical results have been obtained, further critical appraisal of the efficacy, safety, and use of this drug among the broader spectrum of patients will be required. To bridge this knowledge gap, a systematic review and meta-analysis was conducted involving literature from PubMed, Scopus, and Web of Science from January 2018 to November 2024. The studies that were analyzed based on these primary metrics were complete clinical response (cCR), pathologic complete response (pCR), progression-free survival (PFS), overall survival (OS), and safety profile. The process of screening and filtering of abstracts from PubMed, Scopus, and Web of Science generated 1,246 abstracts, of which 28 were included in the final analysis of dostarlimab-gxly treated patients, who totaled 1,567. Results demonstrated a pooled complete response rate of 32.5%, with notably higher pCR rates in deficient mismatch repair (dMMR) tumors compared to mismatch repair-proficient tumors. Patients who received dostarlimab-gxly with radiotherapy or chemotherapy showed higher response rates but increased risks of toxicity. The most common adverse effects were fatigue, diarrhea, and immune-related colitis. The meta-analysis put emphasis on large improvements in PFS and OS compared to control treatments. Dostarlimab-gxly represents a possible alternative treatment strategy for rectal cancer, predominantly effective in the dMMR context. Given its generally balanced safety profile, it is paramount to remain ever vigilant for potential immune-related adverse events. Future work should concentrate on making combination therapies maximally effective, establishing predictive biomarkers, and performing extensive research to further reinforce these findings.