FDA Approves Immunotherapy After Surgery for Stage III Colon Cancer

Keypoints:

• The Food and Drug Administration (FDA) approved Tecentriq (atezolizumab) with chemotherapy on 8 October
• It treats stage III colon cancer with deficient DNA mismatch repair (dMMR) after surgery
• In the ATOMIC trial of 712 patients, the combination cut the risk of recurrence or death by 50%
• Three-year disease-free survival was 86% with the combination and 76% with chemotherapy alone
• It is the first approved adjuvant immunotherapy regimen for this group

The FDA approved Genentech's Tecentriq and its under-the-skin version, Tecentriq Hybreza, for a specific group of colon cancer patients. The drugs are combined with fluoropyrimidine and oxaliplatin chemotherapy. They are given after surgery to people with stage III colon cancer whose tumors are mismatch repair deficient. Roche, Genentech's parent company, announced the decision on 9 October. It is Tecentriq's twelfth US indication.

Stage III means the cancer has reached nearby lymph nodes but not distant organs. Genentech says nearly 25% of colon cancers are diagnosed at that stage. Almost one in three stage III patients experience a recurrence within five years. About 15% of colon cancers are dMMR or have a closely related feature called microsatellite instability-high.

The approval rests on the ATOMIC trial. The National Cancer Institute sponsored it, and the Alliance for Clinical Trials in Oncology led it. It enrolled 712 patients after complete surgery. Adding atezolizumab to the standard mFOLFOX6 chemotherapy cut the hazard of recurrence or death by 50%. The hazard ratio was 0.50. Three-year disease-free survival was 86% against 76%.

The regimen runs for a year. Patients receive atezolizumab with chemotherapy for six months, then atezolizumab alone for six more months. A laboratory test on tumor tissue, called immunohistochemistry, shows whether a tumor is dMMR.

Open questions remain. In the combination arm, 13.6% of patients still had a recurrence within three years, so not every dMMR tumor responds the same way. Whether chemotherapy can be dropped is also unknown. The role of immunotherapy in high-risk stage II disease is uncertain.

Until now, adjuvant treatment for stage III colon cancer did not depend on mismatch repair status. Biomarker testing now steers treatment.