FDA Approves Tecentriq With Chemotherapy After Surgery for Stage III dMMR Colon Cancer

The U.S. Food and Drug Administration has approved Roche unit Genentech's immunotherapy Tecentriq (atezolizumab), in combination with a fluoropyrimidine and oxaliplatin, for the adjuvant treatment of stage III colon cancer with deficient DNA mismatch repair (dMMR), Genentech announced on October 8. The approval also covers Tecentriq Hybreza, the drug's subcutaneous formulation.

Adjuvant treatment is given after surgery to lower the chance that cancer returns. Genentech said the approval is the twelfth U.S. indication for Tecentriq, a monoclonal antibody that binds the PD-L1 protein, and described the regimen as the first approved immunotherapy-based regimen for this setting.

The ATOMIC trial

The approval is based on ATOMIC (A021502), a randomized, open-label, multicenter Phase III trial (NCT02912559) that enrolled 712 patients with stage III dMMR colon cancer. Participants were randomized 1:1 to receive the mFOLFOX6 chemotherapy regimen plus Tecentriq for 12 cycles, about six months, followed by 13 cycles of Tecentriq alone, or to receive mFOLFOX6 alone for 12 cycles. The primary endpoint was disease-free survival.

According to Genentech, adding Tecentriq to mFOLFOX6 reduced the risk of disease recurrence or death by 50% compared with chemotherapy alone. At 36 months, disease-free survival was 86% in the Tecentriq group and 76% in the chemotherapy-only group. The company said the safety profile was consistent with previous studies of Tecentriq and mFOLFOX6. The results were published in The New England Journal of Medicine.

ATOMIC was not a company-run study. Genentech said the trial was sponsored by the U.S. National Cancer Institute and led by the Alliance for Clinical Trials in Oncology, with participation from other groups in the NCI-funded National Clinical Trials Network. Genentech supported it through a Cooperative Research and Development Agreement with the NCI. The trial was led globally by Frank A. Sinicrope of the Mayo Clinic, and German sites took part through the AIO-Studien-gGmbH under Anke Reinacher-Schick of Ruhr-Universität Bochum.

dMMR status was determined by an immunohistochemistry test, such as Roche's VENTANA MMR RxDx Panel, Genentech said.

What the company and investigator said

"This approval provides a new adjuvant treatment option for people with stage III dMMR colon cancer who face a high risk of disease recurrence," said Levi Garraway, Genentech's chief medical officer and head of Global Product Development.

"Until now, the adjuvant standard of care for stage III colon cancer has not differed based on mismatch repair status," said Sinicrope, who is professor of oncology at the Mayo Clinic and U.S. principal investigator for the Alliance ATOMIC trial.

Genentech said about 15% of colon cancer patients have dMMR or microsatellite instability-high tumors, which carry a higher mutation rate. The company also said that nearly 25% of colon cancers are diagnosed at stage III, and that nearly 30% of stage III patients have a recurrence within five years despite surgery and chemotherapy.

Label details

Tecentriq is labeled for this use in adults and children aged 2 and older, while Tecentriq Hybreza is labeled for patients aged 12 and older who weigh at least 40 kg, according to the company. Genentech said safety and effectiveness of Hybreza in younger or smaller children with colon cancer have not been established.

The prescribing information carries warnings for immune-mediated adverse reactions, which the company said can be severe or fatal and can affect organs including the lungs, intestines, liver, hormone glands, kidneys and skin, as well as warnings for infusion-related reactions and complications in patients who have received donor stem cell transplants.