title: First FDA approval of neoadjuvant therapy for breast cancer: pertuzumab for the treatment of patients with HER2-positive breast cancer.
abstract: On September 30, 2013, the FDA granted accelerated approval to pertuzumab (Perjecta; Genentech, Inc.) for use in combination with trastuzumab and docetaxel as neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer. The approval was based in part on a randomized multicenter trial in the indicated population that allocated 417 patients to neoadjuvant treatment with trastuzumab-docetaxel (TD), pertuzumab-trastuzumab-docetaxel (PTD), pertuzumab-trastuzumab, or pertuzumab-docetaxel. PTD was administered preoperatively every 3 weeks for four cycles. Following surgery patients received three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide every 3 weeks and trastuzumab every 3 weeks to complete 1 year of therapy. The pathologic complete response rates by the FDA-preferred definition [absence of invasive cancer in the breast and lymph nodes (ypT0/is ypN0)] were 39.3% and 21.5% in the PTD and the TD arms, respectively (P = 0.0063). The most common adverse reactions with PTD were alopecia, diarrhea, nausea, and neutropenia. This approval was based on the totality of evidence, particularly improved survival in the metastatic breast cancer trial, and a fully accrued confirmatory trial.
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland. Laleh.AmiriKordestani@fda.hhs.gov.
authors.forename: Laleh
authors.initials: L
authors.lastname: Amiri-Kordestani
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Suparna
authors.initials: S
authors.lastname: Wedam
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Shenghui
authors.initials: S
authors.lastname: Tang
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Amy
authors.initials: A
authors.lastname: Tilley
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Amna
authors.initials: A
authors.lastname: Ibrahim
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Robert
authors.initials: R
authors.lastname: Justice
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Patricia
authors.initials: P
authors.lastname: Cortazar
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D017322:Clinical Trials, Phase II as Topic; D005260:Female; D006801:Humans; D020360:Neoadjuvant Therapy / Q000379:methods; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; C485206:pertuzumab