Neoadjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer: primary efficacy analysis of the NOAH trial.

Abstract Abstract #31 Background: Trastuzumab (Herceptin®; H) improves survival in HER2-positive early and metastatic breast cancer. The Phase III NOAH trial is the largest neoadjuvant study that evaluated the addition of H to an anthracyclines- and taxanes-based chemotherapy (CT) for patients (pts) with HER2-positive locally advanced breast cancer (LABC).
 Methods: In this multicentre, randomised, open-label trial, women aged ≥18 years with HER2-positive (IHC 3+ or FISH+) LABC (T3N1 or T4; any T + N2 or N3 or + ipsilateral supraclavicular node involvement) were randomised to receive 3 cycles of doxorubicin (60 mg/m²) and paclitaxel (150 mg/m²) q3w, 4 cycles of paclitaxel (175 mg/m² q3w) and 3 cycles of CMF (cyclophosphamide 600 mg/m², methotrexate 40 mg/m², 5-fluorouracil 600 mg/m² q4w) on Days 1 and 8, with or without concomitant H (8 mg/kg loading dose then 6 mg/kg q3w for 1 year) before surgery. In parallel, LABC pts screened as HER2-negative (IHC 0/1+) received the same CT regimen. The primary end point was event-free survival (EFS), defined as the time between randomisation and disease recurrence or progression, or death from any cause. Secondary end points were pathological complete response (pCR), overall response rate (ORR), overall survival (OS) and safety. We report for the first time here the study's primary endpoint.
 Results: 327 pts were enrolled. Baseline characteristics were balanced for randomised pts. Inflammatory breast cancer was present in 27% of HER2-positive vs 14% of HER2-negative tumours, while 35% vs 64%, respectively, were hormone-receptor positive. EFS was analyzed after 88 events in the HER2-positive group (n=228). EFS rate at 3 years was significantly better in the H + CT arm compared with CT alone: 70.1% vs 53.3%, respectively (HR 0.56; p=0.007). EFS rate in the HER2-negative arm was 67.4%. OS data were immature at this stage. Trastuzumab treatment was the only variable significantly associated with EFS outcome in multivariate analysis which included disease stage and hormonal receptor status. Both ORR and pCR were significantly higher in the H + CT arm compared to CT alone: 89% vs 77% for ORR, respectively (p=0.02); 39% vs 20% for pCR, respectively (p=0.002). Similar results for ORR and pCR were observed between the HER2-positive CT-alone arm and the HER2-negative arm. The addition of H to CT in the neoadjuvant setting was well tolerated with acceptable cardiac safety.
 Conclusion: Neoadjuvant H significantly increased EFS in pts with HER2-positive LABC. This analysis of the NOAH study establishes neoadjuvant H with CT as a standard treatment option in women with HER2-positive LABC. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 31.