Regulatory Decision Summary for Perjeta
Review decision
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
Product type:
Medicinal ingredient(s):
Therapeutic area:
Type of submission:
Control number:
What was the purpose of this submission?
Hoffmann-La Roche Limited filed a Supplemental New Drug Submission for Perjeta (pertuzumab for IV infusion), indicated for use in combination with Herceptin and chemotherapy as an adjuvant treatment for patients with HER2-positive early breast cancer. After reviewing the submitted data package, Health Canada authorized the following indication, Perjeta is indicated in combination with Herceptin and chemotherapy for the adjuvant treatment of patients with HER2-positive early breast cancer with lymph node positive and/or hormone receptor negative disease. This is in addition to the previously authorized indication for metastatic breast cancer (see Product Monograph).
Why was the decision issued?
Perjeta (pertuzumab for IV infusion) is a humanized monoclonal modified immunoglobulin G1 antibody that binds to the human epidermal growth factor receptor 2 (HER2). Through binding to the extracellular domain of HER2, Perjeta inhibits receptor activation.
Authorization of Perjeta was based on the results from a pivotal Phase III study (BO25126, Aphinity). This was a randomized, double-blind, 2-arm, multicenter, placebo-controlled trial with a total of 4804 patients. Patients with operable HER2-positive early breast cancer were randomized to receive either Perjeta plus trastuzumab and chemotherapy (n = 2400) or placebo plus trastuzumab and chemotherapy (n = 2404) as adjuvant therapy. The choice of standard chemotherapy was determined by the investigator for each individual patient. Perjeta was administered, in combination with trastuzumab, once every three weeks for 52 weeks, with an 18 cycle maximum.
The primary efficacy endpoint of this study was invasive disease-free survival (IDFS). Clinical benefit in IDFS was observed in two clinically relevant patient groups, patients with lymph node-positive (LN+) disease and patients with hormone receptor-negative disease. With the addition of Perjeta to adjuvant therapy, patients with LN+ and/or hormone receptor-negative HER2-positive early breast cancer had a 23% and 24% reduction in the risk of recurrent disease or death, respectively.
Overall, the safety of Perjeta observed was consistent with the known profile. A higher incidence of diarrhea, nausea, fatigue, rash and mucosal inflammation occurred in patients receiving Perjeta. Additionally, while the incidence was low (<1%), a higher number of symptomatic cardiac events (cardiac failures or cardiac deaths) occurred in patients treated with Perjeta. These risks have been appropriately captured in the Product Monograph.
The recommended dose of Perjeta is 840 mg for the first IV infusion, with subsequent doses of 420 mg. Perjeta is to be administered once every 3 weeks for a maximum of 18 cycles (see Product Monograph for details).
A Notice of Compliance (NOC) was recommended based on the positive benefit-risk profile.
Decision issued
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.