FDA Approves atezolizumab to Treat dMMR Colon Cancer

The Food and Drug Administration (FDA) has approved atezolizumab (Tecentriq, Genentech, Inc.) in combination with fluoropyrimidine and oxaliplatin for the adjuvant treatment of adult and pediatric patients 2 years of age and older with stage III mismatch repair deficient (dMMR) colon cancer. FDA also approved atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza, Genentech, Inc.) in combination with a fluoropyrimidine and oxaliplatin for the adjuvant treatment of adult and pediatric patients 12 years of age and older who weigh 40 kg or greater with Stage III dMMR colon cancer.

Approval is based on ATOMIC/ML39057 (NCT02912559), a multicenter, randomized, open-label, active-controlled trial in 711 adults and one 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 randomized (1:1) to receive either atezolizumab in combination with mFOLFOX6 (oxaliplatin, leucovorin and fluorouracil) for 12 cycles followed by atezolizumab monotherapy for six months, or mFOLFOX6 alone for 12 cycles. The major efficacy outcome measure was disease-free survival (DFS) as assessed by the investigator. The hazard ratio for the DFS comparison was 0.50 (95% CI: 0.35, 0.73; p-value 0.0001), and the median DFS was not reached (NR) in either arm.

The recommended atezolizumab dose for adult patients is 840 mg every two weeks, 1,200 mg every three weeks or 1,680 mg every four weeks administered intravenously in combination with chemotherapy for six months, followed by atezolizumab as a single agent for six 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 two weeks or 15 mg/kg (up to a maximum of 1,200 mg) every three weeks in combination with chemotherapy for six months, followed by atezolizumab as a single agent for six 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 greater is one 15 mL injection every three weeks (containing 1,875 mg of atezolizumab and 30,000 units of hyaluronidase) administered subcutaneously in combination with chemotherapy for six months, followed by atezolizumab and hyaluronidase-tqjs as monotherapy for six 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.