Journal Article

Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial

Mano, Max, Dafni, Urania, Pritchard, Kathleen I, Piccart-Gebhart, Martine J, Skiadopoulos, George, Cameron, David, Mendiola, Cesar, Jackisch, Christian, Baselga, José, Eckart, Michael J, Gianni, Luca, Goldhirsch, Aron, Semiglazov, Vladimir, Shen, Zhenzhou, Veronesi, Andrea, Pedrini, José Luiz, Smith, Ian, Vrdoljak, Eduard, Bell, Richard, Procter, Marion, Azambuja, Evandro, Gelber, Richard D, Muehlbauer, Susanne, Untch, Michael, Pluzanska, Anna

2011

Overview

Treatment with adjuvant trastuzumab for 1 year improves disease-free survival and overall survival in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. We aimed to assess disease-free survival and overall survival after a median follow-up of 4 years for patients enrolled on the Herceptin Adjuvant (HERA) trial. The HERA trial is an international, multicentre, randomised, open-label, phase 3 trial comparing treatment with trastuzumab for 1 and 2 years with observation after standard neoadjuvant, adjuvant chemotherapy, or both in patients with HER2-positive early breast cancer. The primary endpoint was disease-free survival. After a positive first interim analysis at a median follow-up of 1 year for the comparison of treatment with trastuzumab for 1 year with observation, event-free patients in the observation group were allowed to cross over to receive trastuzumab. We report trial outcomes for the 1-year trastuzumab and observation groups at a median follow-up of 48·4 months (IQR 42·0–56·5) and assess the effect of the extensive crossover to trastuzumab. Our analysis was by intention-to-treat. The HERA trial is registered with the European Clinical Trials Database, number 2005-002385-11. The HERA trial population comprised 1698 patients randomly assigned to the observation group and 1703 to the 1-year trastuzumab group. Intention-to-treat analysis of disease-free survival showed a significant benefit in favour of patients in the 1-year trastuzumab group (4-year disease-free survival 78·6%) compared with the observation group (4-year disease-free survival 72·2%; hazard ratio [HR] 0·76; 95% CI 0·66–0·87; p<0·0001). Intention-to-treat analysis of overall survival showed no significant difference in the risk of death (4-year overall survival 89·3% vs 87·7%, respectively; HR 0·85; 95% CI 0·70–1·04; p=0·11). Overall, 885 patients (52%) of the 1698 patients in the observation group crossed over to receive trastuzumab, and began treatment at median 22·8 months (range 4·5–52·7) from randomisation. In a non-randomised comparison, patients in the selective-crossover cohort had fewer disease-free survival events than patients remaining in the observation group (adjusted HR 0·68; 95% CI 0·51–0·90; p=0·0077). Higher incidences of grade 3–4 and fatal adverse events were noted on 1-year trastuzumab than in the observation group. The most common grade 3 or 4 adverse events, each in less than 1% of patients, were congestive cardiac failure, hypertension, arthralgia, back pain, central-line infection, hot flush, headache, and diarrhoea. Treatment with adjuvant trastuzumab for 1 year after chemotherapy is associated with significant clinical benefit at 4-year median follow-up. The substantial selective crossover of patients in the observation group to trastuzumab was associated with improved outcomes for this cohort. F Hoffmann-La Roche, Michelangelo Foundation.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adult / Antibodies, Monoclonal - therapeutic use / Antibodies, Monoclonal, Humanized / Antineoplastic Agents - therapeutic use / Breast Neoplasms - drug therapy / Breast Neoplasms - metabolism / Breast Neoplasms - pathology / Breast Neoplasms - therapy / Chemotherapy, Adjuvant / Combined Modality Therapy / Female / Follow-Up Studies / Hematology, Oncology and Palliative Medicine / Humans / Middle Aged / Randomized Controlled Trials as Topic / Receptor, ErbB-2 / Survival Analysis / Trastuzumab