Single-center phase 2 trial of nonoperative management of mismatch repair deficient tumors

A phase 2 trial at Memorial Sloan Kettering Cancer Center (New York, NY) investigated the possibility of nonoperative management for mismatch repair deficient (MMRd) tumors. The study included patients with stage 2-3, resectable MMRd cancer who received dostarlimab (anti-PD-1) for six months, in two cohorts. The first cohort included 49 patients with rectal cancer; the second cohort included 54 patients with non-rectal cancers. Patients who experienced clinical complete response could choose not to undergo resection. In the rectal cancer cohort, 100% of 49 patients experienced clinical complete response. In the non-rectal cancer cohort this was the case for 35 of 54 patients (65%). Of the 84 patients in both cohorts who experienced complete clinical response, 82 choose to skip surgery. In the rectal cancer cohort, 92% of patients were still disease-free at two years, and four patients’ complete responses had lasted five years. The authors conclude that in the curative setting, neoadjuvant PD-1 blockade offers the option of nonoperative management for most patients with early stage MMRd malignancies.