Dostarlimab 500mg/10ml solution for infusion vials

Endometrial cancer constitutes a substantial proportion of gynaecological malignancies globally, representing 83% of uterine corpus cancers. With an annual incidence of 60,000 new cases and 11,000 deaths, it is a significant health concern. Emerging molecular therapies, including pembrolizumab and dostarlimab, show promise in advanced cases. This systematic review assesses the efficacy and safety of pembrolizumab and dostarlimab in advanced endometrial cancer. The study adhered to a PROSPERO-registered protocol (CRD42023471455) detailing research questions, objectives, and inclusion/exclusion criteria. A thorough search across multiple databases until October 2023 utilised specific keywords. Inclusion criteria encompassed RCTs and observational studies focusing on female patients with advanced endometrial carcinoma, evaluating pembrolizumab or dostarlimab efficacy and safety. Independent reviewers performed data extraction and quality assessment. The search yielded 16 studies involving 5168 participants, with interventions including pembrolizumab and dostarlimab. The risk of bias varied across studies. Dostarlimab demonstrated significantly improved progression-free and overall survival. Pembrolizumab exhibited a moderate objective response rate. Adverse events, including treatment-related deaths, dose reductions, and discontinuations, were noted for both treatments. Dostarlimab presents promising results with improved survival outcomes, while pembrolizumab exhibits a moderate response rate. The complex nature of treatment outcomes shows the need for more evaluations. Future studies should focus on biomarker identification, validation, and factors contributing to conflicting results. Comparative studies and exploration of combination therapies could enhance understanding and treatment strategies.

Abstract licence: CC BY-NC-ND 4.0

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.

Abstract licence: CC BY-NC-ND 4.0