New Immunotherapy Offers Hope for Rectal Cancer Patients to Avoid Standard Treatments

The U.S. Food and Drug Administration (FDA) has approved dostarlimab (brand name: Jemperli) for the treatment of a specific type of rectal cancer known as microsatellite instability-high (MSI-H)/mismatch repair deficient cancer. This marks a significant advancement in cancer therapy, potentially allowing a subset of patients to avoid the aggressive and life-altering standard treatments.

The newly approved immunotherapy functions as a checkpoint inhibitor, which works by releasing the immune system's natural defenses to identify and attack cancer cells. This approach has shown remarkable efficacy in clinical studies. In a trial involving 154 patients with MSI-H/mismatch repair deficient rectal cancer, 68% achieved a complete clinical response at one year after receiving nine infusions of dostarlimab over six months. A complete clinical response means that tumors were no longer detectable through imaging or other monitoring methods.

"Not only did they reach clinical complete response, but they maintained that for a year," said Dr. Andrea Cercek, section head of colorectal cancer at Memorial Sloan Kettering Cancer Center and principal investigator of the study. "That really suggests that the response is durable and real."

Standard treatment for rectal cancer typically involves a combination of chemotherapy, radiation, and surgery. For many patients, this can necessitate the lifelong use of a colostomy bag and may impact fertility. The approval of dostarlimab offers a less invasive alternative for those whose tumors possess the specific genetic mutations targeted by the drug. "We have patients who would have lost the ability to bear children who have had children because this therapy replaced chemotherapy, radiation, and life-altering surgery in one swoop," stated Dr. Luis Diaz, head of solid tumor oncology at Memorial Sloan Kettering and a trial investigator.

Patients like Kelly Spill and Sascha Roth have benefited from this new approach. Spill, diagnosed with Stage III colorectal cancer in 2020, was initially told she would need chemo, radiation, and surgery, and would likely need a colostomy bag and be unable to have more children. Instead, she joined the dostarlimab trial. By her fourth infusion, scans showed her tumor had shrunk by 50%, and after completing her treatment, she was declared cancer-free. She has since had two children.

Roth, diagnosed in 2019, learned her Stage III cancer was located too low for surgery and unlikely to respond well to chemotherapy. She became the first patient in the immunotherapy trial at Memorial Sloan Kettering. After completing the infusions, her tumor had disappeared, and she did not require further treatment. "I watched my mom and dad go through standard chemo and radiation and anticipated that would be what my treatment was like. It was nothing like that," Roth recalled.

The immunotherapy drug is also approved for certain endometrial cancers with the same genetic mutations. While dostarlimab can be costly, manufacturer GSK offers savings programs to assist eligible patients. Researchers are continuing to investigate optimal methods for monitoring treatment response, exploring advanced imaging and genetic analysis to accurately assess whether tumors have completely disappeared, even if they are not immediately apparent.

"We still have a lot of learning about what complete clinical response means," Cercek noted. "If it looks like the tumor is responding, we need to give it more time with better techniques to determine whether or not the tumor is truly gone."

Dostarlimab is generally well-tolerated, with side effects reported in about 20% of study participants including fatigue, rash, diarrhea, and itching. Many patients, like Roth, found they could continue with their daily activities during treatment.