On October 8, the U.S. Food and Drug Administration (FDA) approved atezolizumab (Tecentriq) in combination with a fluoropyrimidine and oxaliplatin for the adjuvant treatment of adult and pediatric patients aged 2 years and older with stage III mismatch repair–deficient (dMMR) colon cancer. The FDA also approved atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza) in combination with a fluoropyrimidine and oxaliplatin for the adjuvant treatment of adult and pediatric patients aged 12 years and older who weigh 40 kg or more with stage III dMMR colon cancer.
ATOMIC/ML39057
Efficacy was evaluated in ATOMIC/ML39057 (ClinicalTrials.gov identifier NCT02912559), a multicenter, randomized, open-label, active-controlled trial in 711 adults and 1 pediatric patient with stage III dMMR colon cancer after a complete resection of the primary tumor with no evidence of residual lymph node involvement or metastatic disease. Patients were randomly assigned 1:1 to receive either atezolizumab in combination with mFOLFOX6 (oxaliplatin, leucovorin, and fluorouracil) for 12 cycles followed by atezolizumab monotherapy for 6 months, or mFOLFOX6 alone for 12 cycles.
The major efficacy outcome measure was disease-free survival as assessed by the investigator. The hazard ratio for the disease-free survival comparison was 0.50 (95% confidence interval = 0.35–0.73, P = .0001), and the median disease-free survival was not reached in either arm.
The prescribing information includes warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.
Recommended Dosage
The recommended atezolizumab dose for adult patients is 840 mg every 2 weeks, 1,200 mg every 3 weeks, or 1,680 mg every 4 weeks administered intravenously in combination with chemotherapy for 6 months, followed by atezolizumab as a single agent for 6 months or until disease recurrence or unacceptable toxicity. The recommended dose for pediatric patients is 10 mg/kg (up to a maximum of 840 mg) every 2 weeks or 15 mg/kg (up to a maximum of 1,200 mg) every 3 weeks in combination with chemotherapy for 6 months, followed by atezolizumab as a single agent for 6 months or until disease recurrence or unacceptable toxicity, whichever occurs first.
The recommended dosage of atezolizumab and hyaluronidase-tqjs in adults and pediatric patients 12 years of age and older who weigh 40 kg or more is one 15 mL injection every 3 weeks (containing 1,875 mg of atezolizumab and 30,000 units of hyaluronidase) administered subcutaneously in combination with chemotherapy for 6 months, followed by atezolizumab and hyaluronidase-tqjs as monotherapy for 6 months or until disease recurrence or unacceptable toxicity, whichever occurs first. The recommended dosage for pediatric patients under 12 years of age and patients 12 years of age and older who weigh less than 40 kg has not been established.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence which provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, Israel’s Ministry of Health, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. These applications were granted Priority Review.
