Optimising the Duration of Adjuvant Trastuzumab in Early Breast Cancer in the UK

Adjuvant trastuzumab for patients with HER2-positive early breast cancer showed significant improvements in both disease-free and overall survival with 12 months of treatment [1,2], which was approved by the National Institute for Health and Care Excellence (NICE) in the UK in 2006. When the FinHer trial showed similar results with 9 weeks of trastuzumab [3], there was significant interest in whether shorter durations might be as effective. Additional benefits for patients could be less toxicity, fewer hospital visits and a more rapid return to normal life, with considerable societal benefits of reduced costs. PERSEPHONE was the pragmatic UK duration trial funded by the National Institute for Health Research, Health Technology Assessment Programme (NIHR HTA), which showed that 6 months of adjuvant trastuzumab was non-inferior to 12 months with a 4-year disease-free survival rate of 89.4% compared with 89.8% (non-inferiority P = 0.01) [4]. Less toxicity was reported with 6 months, particularly cardiac toxicity, and there were cost savings over the first 2 years [5], which were maintained over an average patient's lifetime when extrapolated using an economic model. After the publication of these results in June 2019, the Optimal Duration of Adjuvant Trastuzumab Working Group was convened, comprising a diverse, multidisciplinary membership. There were representatives from the PERSEPHONE Trial Management Group, including patient advocates, the National Cancer Research Institute (NCRI) Breast Group, the Association of Cancer Physicians, the Royal College of Radiologists and the Independent Cancer Patients' Voice. By November 2019, both dual antibody treatment with trastuzumab and pertuzumab [6] and extended neratinib after single-agent trastuzumab [7] had been approved by NICE, only for those at high risk of recurrence. Therefore, single-agent trastuzumab remained standard of care for those at lower risk of recurrence and recommendations were made for these patients.