Regulatory Decision Summary for Enhertu

Authorization was primarily based on a multicentre, open-label, non-controlled pivotal phase 2 trial U201 in adult patients with unresectable or metastatic HER2-positive breast cancer who had received prior treatment with trastuzumab emtansine (T-DM1). A total of 184 adult patients were enrolled to receive Enhertu monotherapy 5.4 mg/kg every 3 weeks (Q3W) until disease progression, unacceptable toxicity, or withdrawal of patient consent. The primary efficacy endpoint was confirmed objective response rate (ORR) assessed by independent central review (ICR). At the date cutoff for the submission, the ORR was 60.9%. The median duration of response (DoR) was 14.8 months. In the context of the recommended condition of use and the available treatment options, these efficacy results are considered promising evidence of clinical effectiveness.

The safety of Enhertu was evaluated in a pooled analysis of 234 patients with HER2-positive unresectable or metastatic breast cancer who received at least 1 dose of Enhertu at 5.4 mg/kg in the pivotal study U201 and the supportive study J101. The most common adverse reactions (frequency ≥ 20%) were nausea, fatigue, vomiting, alopecia, constipation, decreased appetite, anemia, neutrophil count decreased, diarrhea, cough, leukopenia, headache and platelet count decreased. Serious adverse reactions occurred in 20% of patients. Serious adverse reactions in ≥ 1% of patients were interstitial lung disease (ILD), vomiting, nausea and hypokalemia. Fatalities due to adverse events occurred in 5.1% of patients including ILD (2.6%). Based on non-clinical toxicology findings, Enhertu can cause embryo-fetal toxicity. There is also a risk of medication error between Enhertu and trastuzumab or T-DM1. The safety findings are adequately described in the final approved Product Monograph including the Patient Medication Information.

Enhertu represents a new treatment option for adult patients with unresectable or metastatic HER2-positive breast cancer who have received prior treatment with T-DM1. Based on the evidence reviewed, the benefit/risk profile is considered favorable for Enhertu under the recommended condition of use. The clinical benefit of Enhertu is to be confirmed in an ongoing phase 3 clinical trial U301.

The recommended dose of Enhertu is 5.4 mg/kg given as an intravenous infusion Q3W (21 day cycle) until disease progression or unacceptable toxicity.

Health Canada granted this submission advanced consideration under the NOC/c policy.