ASCO GI 2022 | A Phase II trial: dostarlimab alone for the treatment of dMMR locally advanced rectal cancer

Melissa Lumish, MD, Memorial Sloan Kettering Cancer Center, New York, NY, outlines the Phase II trial exploring a PD-1 blockade for deficient mismatch repair (dMMR) locally advanced rectal cancer. 5-10% of rectal cancers are dMMR and the majority of patients have Lynch syndrome (LS). Although immune checkpoint inhibitors have shown efficacy in treating metastatic dMMR rectal cancer, they have not been investigated in the neoadjuvant setting. In this Phase II trial, 16 patients were recruited, 11 of which completed 6 months of treatment with the PD-1 blockade dostarlimab. The treatment of this patient population was distinct to the standard treatment approach of total neoadjuvant therapy by which patients with locally advanced rectal cancer receive chemotherapy, radiation and surgery. Notably, the 11 patients who achieved CR did not require chemotherapy, radiation nor surgery and are currently on observation undergoing non-operative management. Dr. Lumish emphasizes how this is a unique case due to the 100% CR rate observed whilst being able to spare the morbidity associated with radiation and surgery. A longer-term follow-up will be required to confirm the 11 patients with CR have a durable response and to determine how the remaining patients respond. This interview took place at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium.