The first immunotherapy-based adjuvant therapy for dMMR stage 3 colon cancer
Reduced risk of recurrence or death by 50% in phase 3 clinical trial... 3-year disease-free survival rate 86.3%
Roche's immunotherapy drug 'Tecentriq' has been approved in the United States as an adjuvant treatment after surgery for patients with certain types of stage 3 colon cancer. After removing the tumor, a treatment option was added to lower the risk of recurrence by adding immunotherapy to existing chemotherapy.
On the 8th (local time), the U.S. Food and Drug Administration (FDA) approved the combination of Tecentriq and fluoropyrimidine and oxaliplatin as adjuvant therapy for stage 3 colon cancer with DNA mismatch repair defects (dMMR). Tecentriq, an intravenous formulation, and ‘Tecentriq Hybrezza’, a subcutaneous injection formulation, were included in the approval. According to Genentech, a Roche affiliate, this is the first time that immunotherapy-based postoperative adjuvant therapy has been approved for this patient group.
dMMR refers to a condition in which DNA errors that occur when cells divide are not properly repaired. As these tumors accumulate mutations, it can become easier for the immune system to recognize cancer cells. According to the Mayo Clinic, about 15% of colon cancers have dMMR. Fluoropyrimidine- and oxaliplatin-based chemotherapy has been used as standard adjuvant treatment after surgery for existing stage 3 colon cancer, regardless of MMR status.
The phase 3 clinical trial ‘ATOMIC’, which is the basis for approval, evaluated the effect of adding Tecentriq to existing chemotherapy in 712 dMMR stage 3 colon cancer patients who underwent surgery. The anticancer therapy used clinically is mFOLFOX6, which is a combination of fluorouracil, a fluoropyrimidine drug, plus oxaliplatin and leucovorin.
In the combination group, mFOLFOX6 and Tecentriq were administered for 6 months, followed by Tecentriq monotherapy for 6 more months. The control group was administered only mFOLFOX6 for 6 months. The main evaluation indicator was disease-free survival, which is the period from the time patients were assigned to the two groups until recurrence or death.
According to results published in the international journal New England Journal of Medicine (NEJM), at a median follow-up period of 40.9 months, the risk of recurrence or death in the combination group was 50% lower than that of the chemotherapy alone group. The 3-year disease-free survival rate, which represents the proportion of patients who survived without recurrence, was 86.3% in the combination group and 76.2% in the single group, a difference of 10.1 percentage points. However, no statistically significant difference in overall survival (OS) was confirmed at the time of the analysis reported in the paper, and additional follow-up is necessary to evaluate the long-term survival effect.
Grade 3 to 4 adverse reactions occurred in 84.1% of the combination group and 71.9% of the single group. The FDA stated that the product's prescription information includes warnings and precautions regarding immune-mediated adverse reactions and injection-related reactions.
Dr. Frank Sinikloff of Mayo Clinic, who led the study, explained that ATOMIC is the first study to demonstrate the effectiveness of immunotherapy in patients with dMMR stage 3 colon cancer whose tumors were surgically removed. He stated that the goal of treatment is to reduce recurrence and increase the chance of cure by removing microscopic cancer cells that may remain after surgery.
With this approval, the number of indications for Tecentriq in the U.S. increased to 12. Roche plans to pursue related approval procedures in other regions, including the European Medicines Agency (EMA).
