FDA Approves Immunotherapy Regimen Studied by Mayo Clinic for Stage 3 Colon Cancer

The Food and Drug Administration (FDA) has approved the immunotherapy drug atezolizumab in combination with chemotherapy for some patients with stage 3 colon cancer following surgery. The treatment is for patients whose tumors have deficient DNA mismatch repair, or dMMR.

The approval is based on results from the ATOMIC clinical trial led by Mayo Clinic. The study found that adding atezolizumab to standard chemotherapy reduced the risk of cancer recurrence or death by 50% compared with chemotherapy alone. FDA approval further establishes the addition of immunotherapy to chemotherapy as a standard treatment option in the curative setting and helps to make it more readily accessible to patients who may benefit.

"This approval represents a major advance for patients with a subset of stage 3 colon cancer," says Frank Sinicrope, M.D., a Mayo Clinic oncologist and leader of the ATOMIC study. "ATOMIC is the first study to show the benefit of immunotherapy after surgical resection in patients with locally advanced colon cancer with dMMR. The goal after surgery is to eliminate remaining microscopic cancer cells responsible for recurrence and thereby increase the number of patients who are cured of their disease."

The phase 3 ATOMIC trial enrolled 712 patients with stage 3 dMMR colon cancer that had been surgically removed and spread to regional lymph nodes. Patients were randomly assigned to receive standard chemotherapy alone or chemotherapy combined with atezolizumab, an immune checkpoint inhibitor, followed by additional atezolizumab.

At three years, 86.3% of patients who received immunotherapy plus chemotherapy were alive and free of disease, compared with 76.2% of patients who received chemotherapy alone. The findings were published this year in The New England Journal of Medicine.

Moving Immunotherapy Earlier in Treatment

Immune checkpoint inhibitors have transformed the treatment for several advanced cancers. In colon cancer, they have been particularly effective against tumors with dMMR. These tumors have a defect in their ability to properly repair errors in their DNA during cell division, leading to the accumulation of multiple mutations that can make the cells more recognizable to the immune system.

Before the ATOMIC trial, immunotherapy was used primarily for advanced or metastatic dMMR colorectal cancer. ATOMIC examined whether activating the immune system after surgery that is intended to cure the patient could prevent cancer from returning.

"Instead of waiting until a patient's colon cancer has returned or spread, we can now use immunotherapy earlier when patients have undergone surgery and are able to prevent or markedly reduce the chance of recurrence," Dr. Sinicrope says.

Approximately 15% of colon cancers have dMMR. Testing a patient's tumor can identify dMMR and help determine the optimal treatment.

An Important Advance for Younger Patients

The approval also comes as colorectal cancer rates among younger adults continue to rise. More than one-quarter of patients enrolled in ATOMIC were younger than 50.

The trial included patients with Lynch syndrome, the most common inherited cause of colorectal cancer and the most common hereditary cancer syndrome. People with Lynch syndrome have an increased risk of developing several cancers, particularly colorectal cancer, and frequently develop cancer at younger ages. Colon cancers associated with Lynch syndrome generally have dMMR.

"For patients who develop colon cancer at a young age, preventing recurrence can translate into decades of life gained," Dr. Sinicrope says. "Being able to offer an effective treatment such as immunotherapy to improve the survival of these patients is especially meaningful for them and their families."

From Scientific Insight to a New Treatment

ATOMIC grew from years of research into the biology of dMMR colon cancer. Dr. Sinicrope and colleagues previously observed that these tumors contain large numbers of inflammatory and immune cells, including those cells targeted by immune checkpoint inhibitors. Those findings provided the scientific rationale for testing whether immunotherapy could strengthen the body's immune response against cancer cells that can remain after surgery.

Dr. Sinicrope developed the study, which was conducted through the Alliance for Clinical Trials in Oncology, part of the National Cancer Institute-supported National Clinical Trials Network. Patients from the U.S. and Germany participated.

"The patients who participated in ATOMIC made this advance possible, and their contribution will change how we treat patients with dMMR colon cancer here and around the world," says Dr. Sinicrope.

The National Comprehensive Cancer Network previously updated its guidelines to include atezolizumab plus chemotherapy as a treatment option based on the ATOMIC findings. FDA approval establishes the regimen as an approved treatment for eligible patients in the U.S.

The National Cancer Institute of the National Institutes of Health and Genentech funded the ATOMIC study. See the study in The New England Journal of Medicine for a complete list of authors, disclosures and funding.