OT1-02-04: Adjuvant Pertuzumab and Herceptin IN IniTial TherapY of Breast Cancer: APHINITY (BIG 4–11/BO25126/TOC4939g).
Authors: von Minckwitz G , Baselga J , Bradbury I , de Azambuja E , Scullion MJ , Ross G , Saini KS , Piccart-Gebhart M 
Published: June 2012

Abstract
Background
Approximately 20% of breast cancer (BC) patients (pts) have HER2−positive tumors. While the adjuvant use of the anti-HER2 humanized monoclonal antibody trastuzumab (T) has been shown to improve disease-free (DFS) and overall survival (OS), not all pts treated with this agent benefit from this therapy. Pertuzumab (P) is a humanized monoclonal antibody that inhibits HER2 dimerization and induces ADCC with a complementary mechanism of action to T. In HER2−positiveadvanced BC, T and P is active in pts who have progressed to T. In the neoadjuvant setting, T and P in combination with chemotherapy (CT) nearly doubled the pathological complete response rate compared to either T or P administered in combination with CT (45.8% vs 29% vs 24%, respectively). Therefore, comprehensive HER2 blockade with two anti-HER2 monoclonal antibodies warrants further investigation in the adjuvant setting.
Trial Design: APHINITY is a prospective, randomized, multicenter, double-blind, placebo-controlled study in pts with HER2−positive primary BC who have had an excision of their tumor. Pts will be randomized to one of 2 arms (1:1 ratio). The investigational arm will comprise of a course of adjuvant CT (investigators choice) consisting of either an anthracycline-taxane or taxane-platin containing regimens and T and P for 1 year. The comparator arm will consist of the same adjuvant CT backbone with T and placebo for 1 year.
Major Eligibility Criteria:
1. Non-metastatic primary BC histologically confirmed and adequately excised
2. Node-positive or node-negative: for patients with node-positive disease (pN ≥1), any pT except T0; for patients with node-negative disease (pN0), tumor size must be &gt;1.0 cm OR for tumor size between &gt;0.5 cm and ≤1.0 cm, at least one of the following features will be required: histologic grade 3 OR negative for ER and PgR OR age &lt;35 years
3. The interval between definitive surgery for BC and randomization must be at least 3 weeks but no more than 7 weeks
4. Baseline LVEF ≥55%
5. HER2−positive BC confirmed by a central laboratory and defined as: IHC 3+ in &gt;10% immunoreactive cells OR HER2 gene amplification by in situ hybridization [ISH] (ratio of HER2 gene signals to centromere 17 signals ≥2)
Aims: The primary objective is to compare invasive disease-free survival (IDFS) between both treatment arms. Secondary objectives include comparing IDFS including second non-BC, DFS, OS, recurrence-free interval (RFI), distant RFI, cardiac safety, overall safety and health-related quality of life in the two treatment arms.
Statistical Methods: Pts will be stratified based on nodal status, type of adjuvant CT regimen, hormone receptor status and geographical region. The study is designed to have an 80% power to test the null hypothesis of no true difference in risk of an IDFS event (HR = 1) versus the alternative hypothesis of a difference (HR = 0.75) in hazard rates with a 5%, 2-sided significance level.
Target accrual: 3806; Present accrual: Start Q4 2011
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-02-04.