The results will be presented at the 2018 American Society of Clinical Oncology (ASCO) meeting beginning June 4, in Chicago, in a presentation titled “PERSEPHONE: 6 versus 12 months (m) of adjuvant trastuzumab in patients (pts) with HER2 positive (+) early breast cancer (EBC): Randomised phase 3 non-inferiority trial with definitive 4-year (yr) disease-free survival (DFS) results.”
Approximately one in five patients with breast cancer is positive for human epidermal growth factor receptor 2 (HER2). HER2-positive is a term used to describe cancer cells that express high levels of this cell-surface protein, leading to increased tumor growth and potential to spread.
Herceptin, from Genentech, is an approved immunotherapy for this aggressive type of breast cancer – as a single treatment or in combination with chemotherapy. Herceptin binds to HER2, blocking its function and leading to cell death. Among the therapy’s adverse effects, heart damage (cardiomyopathy) has been the most concerning.
The standard Herceptin therapy takes 12 months, but its optimum duration has been debated, as some studies have suggested that a similar efficiency could be achieved with a shorter treatment. Reducing treatment duration is always a goal, as it can ease patients’ burden, overall costs, and potentially the occurrence of adverse effects.
A randomized multicenter Phase 3 clinical trial called PERSEPHONE (NCT00712140) evaluated whether a six-month Herceptin therapy would be as effective as the 12-month therapy.
The study’s primary goal was to compare disease-free survival (DFS) – the time a patient lives without cancer relapse
– between the two durations of treatment. To be considered non-inferior, the DFS of the six-month treatment should be less than 3% lower than the 12-month’s DFS.
PERSEPHONE included 4,089 women with HER2-positive, early-stage breast cancer, who were randomized to receive Herceptin either for six or 12 months. The women were given standard chemotherapy during the trial and were followed for a median of 4.9 years.
The disease-free survival rate at four years was 89.4% with six months of therapy and 89.8% with 12 months of therapy. The overall survival was also similar between the two treatment groups.
Another important finding was a significant reduction of heart-related adverse events with the shorter treatment, with only 4% of women stopping treatment early due to heart problems, compared with 8% of those receiving standard treatment
This was the largest trial to examine the impact of shortening the duration of Herceptin treatment so far, the researchers said, and results showed that treatment for six months was just as efficient as the 12-month treatment and reduced the incidence of heart-related side effects.
“We are confident that this will mark the first steps towards a reduction of the duration of trastuzumab treatment to 6 months in many women with HER2-positive breast cancer,” Helena Earl, MD, the study’s lead author, said in a press release.
The researchers are performing additional analysis on the PERSEPHONE data to determine the impact of treatment duration on patients’ quality of life, as well as cost-effectiveness
They also plan to use blood and tissue samples taken from patients during the trial to find biomarkers that can help predict which patients will respond well to a shorter treatment.