Andrea Cercek, MD, on Rectal Cancer: Durable Complete Responses to PD-1 Blockade Alone

We're presenting data on the durability of clinical complete responses in mismatch repair-deficient locally advanced rectal cancer to PD-1 therapy alone. We designed a phase II clinical trial of neoadjuvant PD-1 blockade with dostarlimab in mismatch repair-deficient rectal cancer, with the idea that we could use immunotherapy alone, dostarlimab alone to treat locally advanced rectal cancer, and potentially omit standard approaches to therapy, including chemotherapy, radiation, and surgery. And we initially presented the data two years ago. In June of 2022, we noted complete responses, 100% complete responses in 14 consecutive patients. So now we're presenting the expanded data. The trial has been ongoing, and we continue to see a hundred percent complete clinical responses now in 42 patients treated with dostarlimab. None of our patients have needed chemotherapy, radiation, or surgery. The second primary endpoint of the trial was the durability of these complete responses. And we have seen now that 24 patients have had more than a year of complete clinical responses after completion of dostarlimab. Really showing that not only are we seeing 100% complete responses, but that these responses are in fact durable in patients. And in terms of quality of life, this has been incredibly impactful for patients. None have needed chemotherapy, radiation, or surgery. And we've seen very little toxicity, only grade 1 or 2 toxicity on trial to dostarlimab, so the patient's quality of life is maintained after treatment. There is now a global study called AZUR-1 with the same exact design, looking at neoadjuvant therapy with dostarlimab in mismatch repair-deficient rectal cancer. Which is a registration study that will hopefully provide care to all patients with early-stage mismatch repair-deficient rectal cancer, and change the standard of care in this population.