Reducing the duration of trastuzumab treatment may be beneficial for women with HER2-positive breast cancer: In the phase III PERSEPHONE trial, women who received the drug for 6 months had a similar rate of disease-free survival as women on a 12-month course, but were half as likely to stop treatment due to cardiac side effects.
Halving the duration of adjuvant trastuzumab (Herceptin; Genentech) treatment may be beneficial for women with early-stage, HER2-positive breast cancer: Those treated with the drug for 6 months had a similar rate of disease-free survival as, and fewer side effects than, those treated for 12 months, according to data presented during a media preview for the 2018 American Association of Clinical Oncology (ASCO) Annual Meeting, held June 1–5 in Chicago, IL (J Clin Oncol 2018;36, no. 15_suppl:506).
Trastuzumab, which targets HER2, received FDA approval in 2006 for the treatment of HER2-positive breast cancer. On the basis of the results of three large phase III trials, the duration of treatment was set at 12 months. However, the same year, a Finnish trial that included 232 women with HER2-positive disease reported that those who received 9 weeks of adjuvant trastuzumab were less likely to experience disease recurrence during 3 years of follow-up than those who didn't receive the drug (N Engl J Med 2006;354:809–20).
To investigate further, British researchers initiated the phase III PERSEPHONE trial in 2007. The goal was to determine “whether women do just as well, or are no worse off, if they take the drug for 6 months instead of 12 months,” explained Helena Earl, MD, of the University of Cambridge in the UK, who presented the results.
Researchers enrolled 4,088 women with early-stage, HER2-positive breast cancer and assigned them to receive nine cycles of trastuzumab over 6 months, or 18 cycles over 12 months, given with or after chemotherapy. Overall, they found that at 4 years, the disease-free survival rate was 89.4% in the 6-month group, compared with 89.8% in the 12-month group. In addition, half as many women treated for 6 months, compared with 12 months, had to stop the drug early due to cardiac side effects (4% vs. 8%).
“This is a very important study for helping our patients live longer and live better,” said Bruce Johnson, MD, chief clinical research officer at Dana-Farber Cancer Institute in Boston, MA. “By reducing [treatment time] by half, they were able to cut down on the number of people that had to stop treatment by half, and certainly we anticipate that this obviously will have an effect on cost as well.”
Richard Schilsky, MD, chief medical officer of ASCO, pointed out that although the early results of the study are promising, 4 years of follow-up is relatively short for breast cancer, and the study does not yet have data on overall survival.
“I think we need to allow time for the data to mature,” he said. Even so, “I find the results quite compelling, and I think it is likely that it will signal a shift … toward shorter duration of [trastuzumab] adjuvant therapy.”
As the PERSEPHONE trial continues, Earl and her team will also analyze blood and tissue samples to find biomarkers for subgroups of women who may benefit from the shorter or longer courses of treatment.
“I think that at the moment we do need to wait for longer follow-up and we need to take a real close look at the data,” Earl said, “but what we hope is that, for many women, this will become standard of care.” –Catherine Caruso
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