ASCO GI 2022 | The remaining challenges surrounding the use of immunotherapy to treat patients with rectal cancer

Melissa Lumish, MD, Memorial Sloan Kettering Cancer Center, New York, NY, talks on the remaining unaswered questions regarding the use of immunotherapy to treat patients with rectal cancer. Dr. Lumish questions whether immune checkpoint inhibitors as a monotherapy will be able to offer a durable response for patients with deficient mismatch repair (dMMR) locally advanced rectal cancer. Patients are having an exceptional initial response to immunotherapy alone in a Phase II trial but a longer term follow-up will be required to confirm that chemotherapy, radiation and surgery can be spared in this patient population. Additionally, there is uncertainty surrounding the role of immunotherapy in non-dMMR disease. To date, the data has been insufficient in exhibiting effectiveness of immunotherapy for patients with proficient mismatch repair disease. Several studies are exploring the manipulation of non-dMMR tumors to resemble dMMR tumors as a means of improving the responsiveness of immune checkpoint inhibitors in patients with non-dMMR disease. There are further questions regarding the optimal time during the course of the disease to treat dMMR locally advanced rectal cancer with immune checkpoint inhibitors. The hypothesis being investigated in the Phase II trial is that providing patients with immune checkpoint inhibitors early during the course of disease progression, prior to receiving chemotherapy or radiation, allows for the exploitation of the immune system. Early interception with immunothepry may prevent any immune escape that can result in resistance to immune checkpoint inhibitors due to the selective pressures of chemotherapy and radiation. This interview took place at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2022.