While 12 months of adjuvant trastuzumab has become the standard of care for women with human epidermal growth factor receptor 2 positive (HER2+) early breast cancer, results from a large international study presented at the 2018 American Society of Clinical Oncology Annual Meeting in June indicate that that duration needlessly increases risk of toxicities.

Twelve months became the de facto standard length of trastuzumab therapy based on the initial registration trials for the drug. Smaller trials have subsequently indicated that shorter periods of exposure to trastuzumab could provide the same benefits. The PERSEPHONE investigators sought to definitively determine whether a significantly compressed course of therapy offered equal disease-free survival benefit as the year-long standard.

Breast Cancer Cell. (Source: Wikipedia.) 

The phase 3 trial randomized 4089 women with HER2+ early breast cancer treated at 152 sites in the United Kingdom to receive either six or 12 months of adjuvant trastuzumab following chemotherapy. Nearly 70% of patients had estrogen-receptor positive disease, according to the study.

At four years, the disease-free survival was 89% in both arms of the trial. The researchers calculated that reducing trastuzumab therapy to six month increased the risk of disease progression or death by 5%, well within the non-inferiority margin.

Halving the exposure to trastuzumab also cut the risk of cardiac events in half, reducing the percentage of patients who stopped treatment because of cardiotoxicity from 8% in the 12-month arm to 4% among those receiving the drug for just six months.

“Given cardiac and other toxicities during months 7-12 of treatment, our results would support a reduction of standard trastuzumab duration to 6 months,” the researchers concluded.