Dual Targeting of HER2-Positive Breast Cancer

In patients with HER2-positive breast cancer, dual targeting of the HER2 pathway has proven to improve survival in the metastatic setting and pathologic complete remission rate (pCR) in the neoadjuvant setting.

To determine if the pCR improvement in the adjuvant setting would translate to improved outcome, investigators conducted an industry-funded, international, randomized, double-blind, placebo-controlled, phase III trial (APHINITY) involving 4805 patients with HER2-positive breast cancer, of whom 63% had node-positive disease and 36% had hormone-receptor–negative disease. Patients received standard adjuvant taxane-based chemotherapy and 1 year of trastuzumab plus either pertuzumab or placebo.

At a median follow-up of 45 months, 3-year invasive-disease–free survival (IDFS; the primary endpoint) was improved with pertuzumab versus placebo (94.1% vs. 93.2%; hazard ratio, 0.81; P=0.045), as it was among those with node-positive disease (92.0% vs. 90.2%; P=0.02). IDFS was similar with pertuzumab or placebo among patients with node-negative disease, (97.5% and 98.4%, respectively), as well as among those with hormone-receptor–positive disease (94.8% and 94.4%) and hormone-receptor–negative disease (92.8% and 91.2%). Cardiac toxicity was similar with both treatments, but grade 3 or higher diarrhea occurred more frequently with pertuzumab (9.8% vs. 3.7%), almost exclusively during chemotherapy.