The current standard of care for women with early, HER2-positive breast cancer is 12 months of trastuzumab. Analysis of the phase 3 randomized clinical trial PERSEPHONE showed that 6 months of treatment with trastuzumab was noninferior to 12 months in terms of disease-free survival. Furthermore, the shorter course of trastuzumab was associated with a 50% reduction in cardiotoxicity leading to cessation of therapy.
These findings, plus the reduced costs associated with 6 months versus 12 months of treatment with trastuzumab, suggest that 6 months of treatment will become the standard of care—once the peer-review publication is available, said experts.
“The PERSEPHONE trial’s researchers worked closely with patient advocates. Everyone involved in the study is very excited by these results,” said lead investigator Helena M. Earl, MBBS, PhD, FRCP, Professor of Clinical Cancer Medicine, University of Cambridge, England, who presented the results at ASCO 2018.
“We are confident that this will mark the first steps toward a reduction of the duration of trastuzumab in many women with HER2-positive breast cancer,” she added.
Approximately 15% of women diagnosed with breast cancer fall into the category of early, HER2-positive breast cancer. Standard trastuzumab therapy reduces cancer recurrence by 40% and breast cancer–specific death by 34%. Smaller studies have suggested that a shorter course of trastuzumab therapy may be as effective as 12 months.
PERSEPHONE was funded by the National Institute for Health Research in the United Kingdom and is the largest trial to date to analyze the effect of shorter-course trastuzumab in this setting.
Study Details
PERSEPHONE enrolled 4089 women with early-stage, HER2-positive breast cancer. The median age was 56 years (range, 23-82 years). The 4-year disease-free survival rate was 89.4% in women who received 6 months of trastuzumab versus 89.8% with 12 months of therapy, an insignificant, minimal difference. In addition, shorter-course trastuzumab was associated with improved cardiac safety: cardiac events led to cessation of therapy in 4% of women who received 6 months of trastuzumab versus 8% of those in the 12-month arm (P <.0001).
All women enrolled in the study received concurrent or sequential chemotherapy in addition to trastuzumab. The median follow-up was more than 5 years. Future data analysis will focus on the effect of a shorter versus longer course of treatment on the patient’s quality of life and costs. A 12-month course of trastuzumab is estimated to cost $76,000.
Longer follow-up is needed to establish survival data in both trial arms before 6 months of trastuzumab can be considered the standard of care.
“This study establishes the noninferiority of 6 months of trastuzumab. Reducing the course of trastuzumab by half can cut down the percentage of people who have to stop due to cardiotoxicity by 50%, and will reduce cost as well,” said Bruce E. Johnson, MD, ASCO President and Chief Clinical Research Officer, Dana-Farber Cancer Institute, Boston, MA, who moderated a press briefing during which this study was featured.
New Standard of Care?
“We need a more detailed look at the data. We need to be cautious before saying 6 months is enough,” Dr Earl said when asked whether 6 months should be considered a new standard of care.
ASCO’s Chief Medical Officer, Richard L. Schilsky, MD, agreed.
“We have no data on overall survival. The survival is relatively short, and we need more mature results. I find the results of PERSEPHONE compelling. Time will tell,” Dr Schilsky said.
“I agree,” said Dr Johnson. “At 5-year follow-up, <10% are dead. These patients were effectively treated, and only 12% relapsed. The cardiotoxicity benefit is clear, but we need to be circumspect about changing practice,” he added.
“Patients report other grade 3 and 4 side effects of trastuzumab that impact their lives. A shorter course would cut down on side effects and make it easier to return to work,” Dr Johnson noted.
