FDA Approves Dostarlimab for dMMR Stage II-III Rectal Cancer, Sparing 72% From Multimodal Therapy in Early Trial Data

The pivotal data came from a non-randomized study in which patients received up to nine doses of dostarlimab every three weeks. Primary endpoint was clinical complete response allowing omission of standard therapy; 72% achieved this at interim analysis. An earlier Memorial Sloan Kettering cohort of 50 patients reported 100% complete response at six months, with one recurrence among 27 followed three years or longer. Both studies enrolled only dMMR/MSI-high tumors confirmed by immunohistochemistry or PCR.

Standard care for locally advanced rectal cancer produces durable local control but carries 20-40% rates of bowel, sexual, and fertility dysfunction plus permanent colostomy in up to 15%. The new regimen targets the 5-10% of rectal cancers with deficient mismatch repair, where high mutational burden increases neoantigen presentation and PD-1 responsiveness. Observational series and the phase 2 data suggest organ preservation is feasible, yet no direct randomized comparison to chemoradiation plus total mesorectal excision yet exists.

GSK must submit confirmatory long-term outcomes under accelerated approval. Pending questions include five-year recurrence rates, late toxicity of immunotherapy, and whether ctDNA or endoscopic surveillance can safely replace imaging. A phase 3 trial comparing dostarlimab to standard care is required to quantify absolute benefit and identify non-responders who still need multimodal therapy.