The dual HER blockade with trastuzumab and pertuzumab in HER2-positive early breast cancer patients has been confirmed to have a positive benefit/risk ratio by the final analysis of the randomized phase III PEONY trial, recently published on Nature Communications.

The randomized, multicenter, double-blind, placebo-controlled phase III PEONY trial was conducted to compare the efficacy, safety, and tolerability of adding pertuzumab to trastuzumab and docetaxel in the neoadjuvant and adjuvant setting in 329 patients with HER2-positive early or locally advanced breast cancer. Patients received neoadjuvant pertuzumab/placebo with trastuzumab and docetaxel, followed by adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide, then pertuzumab/placebo with trastuzumab until disease recurrence or unacceptable toxicity, for up to 1 year. The final analysis of long-term efficacy at 3 and 5 years in PEONY includes data from the adjuvant treatment period, overall treatment period, and treatment-free follow-up period, as well as the prespecified secondary endpoints of event-free survival, disease free survival, overall survival and safety. Both event-free survival and disease free survival rates at 3 and 5 years are shown to be higher in the pertuzumab arm compared with the placebo arm: 5-year event-free survival estimates are 84.8% with pertuzumab and 73.7% with placebo, 5-year disease-free survival rates are 86.0% and 75.0%, respectively. A positive trend towards improved overall survival is seen with pertuzumab compared with placebo, and safety data are in line with the known pertuzumab safety profile and generally comparable between arms. «In patients with early-stage or locally advanced HER2-positive breast cancer, the magnitude of clinical benefit and the acceptable safety profile in PEONY confirms the positive benefit:risk ratio of dual pertuzumab–trastuzumab neoadjuvant/adjuvant therapy, adding to the totality of the evidence of its use in the early setting, irrespective of time of surgery», authors conclude.