Six versus 12 months of adjuvant trastuzumab in combination with dose-dense chemotherapy for women with HER2-positive breast cancer: a multicenter randomized study by the Hellenic Oncology Research Group (HORG).

BACKGROUND: Adjuvant trastuzumab in combination with chemotherapy improves survival of women with HER2-positive early breast cancer. In this study, we compared 12 versus 6 months of adjuvant trastuzumab. PATIENTS AND METHODS: Axillary node-positive or high-risk node-negative women with HER2-positive early breast cancer were randomized to receive 12 or 6 months of adjuvant trastuzumab concurrently with dose-dense, granulocyte colony-stimulating factor (G-CSF)-supported docetaxel (75 mg/m(2) every 14 days for four cycles). All patients received upfront dose-dense, G-CSF-supported FEC (5-fluorouracil 700 mg/m(2), epirubicin 75 mg/m(2), cyclophosphamide 700 mg/m(2) every 14 days for four cycles). Randomization was carried out before commence of chemotherapy. The primary end point was the 3-year disease-free survival (DFS). RESULTS: A total of 481 patients were randomized to receive 12 months (n = 241) or 6 months (n = 240) of adjuvant trastuzumab. Chemotherapy was completed in 99% and 98% of patients, while trastuzumab therapy in 100% and 96% of patients in the 12- and 6-month groups, respectively. After 47 and 51 months of median follow-up, there were 17 (7.1%) and 28 (11.7%) disease relapses in the 12- and 6-month groups (P = 0.08). The 3-year DFS was 95.7% versus 93.3% in favor of the 12-month treatment group (hazard ratio = 1.57; 95% confidence interval 0.86-2.10; P = 0.137). There was no difference in terms of overall survival and cardiac toxicity between the two groups. CONCLUSIONS: Our study failed to show noninferiority for the 6-month arm. The results further support the current standard of care that is administration of adjuvant trastuzumab for 12 months.