Earl HM, et al. - In this open-label, phase 3, non-inferiority, randomized trial, researchers compared the impact of 6-month adjuvant trastuzumab treatment vs standard 12-month treatment on disease-free survival in patients with HER2-positive early breast cancer. In these patients, non-inferiority of 6-month trastuzumab treatment was demonstrated in comparison to 12-month treatment, with less cardiotoxicity and fewer severe adverse events. Based on these findings, the researchers suggested consideration of reduced duration trastuzumab for women at similar risk of recurrence as to those included in the trial.

Methods

• Study participants included adults with HER2-positive early breast cancer and a clear indication for chemotherapy were recruited from 152 centers in the United Kingdom.
• Using a computerized minimization process (1:1), participants were randomized to receive either 6-month or 12-month trastuzumab administered every 3 weeks intravenously (loading dose of 8 mg/kg followed by maintenance doses of 6 mg/kg) or subcutaneously (600 mg), which was given in combination with chemotherapy (concurrently or sequentially).
• Analyzed by intention to treat, disease-free survival was the primary endpoint, with a non-inferiority margin of 3% for 4-year disease-free survival.
• All patients who received trastuzumab were assessed for safety.

Results

• Between October 4, 2007, and July 31, 2015, 2,045 patients received 12-month trastuzumab treatment and 2,044 received 6-month treatment (one patient was excluded because they were double randomized).
• Both treatment groups were followed up for a median of 5.4 years.
• Among those in the 6-month and 12-month treatment groups, 13% and 12%, respectively, experienced a disease-free survival event during the follow-up period.
• In the 6-month group and in the 12-month group, the 4-year disease-free survival was 89.4% and 89.8%, respectively, demonstrating non-inferiority of the 6-month treatment.
• Compared with those who receive 12-month trastuzumab, those who were treated with 6-month trastuzumab reported fewer severe adverse events or early discontinuation due to cardiotoxicity.