Wayne Kuznar, for MDLinx | June 26, 2018
Trastuzumab for 6 months is as effective as the current standard of 12 months as adjuvant treatment for women with HER2-positive early-stage breast cancer, according to data from the phase 3 PERSEPHONE trial, which showed that disease-free survival (DFS), was noninferior with 6-month treatment compared with 12-month treatment, with lower toxicity. Results from the study were presented by Helena Earl, MD, at the 2018 meeting of the American Society of Clinical Oncology (ASCO) in Chicago, IL.
“We believe that these exciting results mark the first steps to the reduction of treatment duration for many women with HER2-positive breast cancer,” said Dr. Earle, professor of clinical cancer medicine, University of Cambridge, United Kingdom.
In 2005, paradigm-shifting results showing significant benefit to 12 months of adjuvant trastuzumab were published, followed by a Cochrane review in 2012 that demonstrated 40% fewer cancer recurrences and 34% fewer deaths with adjuvant trastuzumab. These results were confirmed in longer term follow-up from definitive adjuvant trastuzumab trials.
These data opened the question as to optimal duration of trastuzumab.
“The pivotal licensing trials used 12 months on an empirical basis,” Dr. Earle said. “However, in 2006, the FinHER study showed similar outcomes with just 9 weeks of trastuzumab used concurrently with docetaxel up front. So the world was very interested in knowing whether reduced-duration trastuzumab would have similar outcomes.”
These data formed the basis for the design of the PERSEPHONE trial, which included 4,088 women (67% aged over 50 years) with HER2-positive early breast cancer who were randomized to 6 months (9 cycles) or 12 months (18 cycles) of trastuzumab. All patients had a clear indication for chemotherapy, either anthracycline-based or taxane-based or a combination of both. Trastuzumab could be given concurrently with chemotherapy or sequentially. The trial was conducted at 152 sites in the UK.
DFS was defined as the time from diagnosis to first invasive relapse, (local or distant) or death.
In all, 69% of patients enrolled were estrogen receptor-positive and 59% were node negative. About half of the patients had tumors ≤ 2 cm in size. In all, 42% of patients received anthracycline chemotherapy, 48% received anthracycline with taxanes, and 10% received taxanes only.
Compliance “was better for the 6-month patients, with 90% of patients receiving all cycles of treatment, compared with 82% in the 12-month arm,” said Dr. Earle.
After a median follow-up of 5.4 years, the DFS rates were 89.4% with 6 months of therapy compared with 89.8% with 12 months of therapy. The noninferiority P value was 0.01, “demonstrating noninferiority for the primary endpoint for 6 months trastuzumab versus 12,” she said.
Only 4% of women in the 6-month arm stopped treatment due to cardiotoxicity compared with 8% in the 12-month arm.
“Random effects modeling showed that cardiac function did recover, but recovered more quickly in the 6-month patients,” Dr. Earle said.
Cough, pain, fatigue, chills, and palpitations were significantly more common in the 12-month arm. Quality of life and economic analyses are ongoing.
“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,” concluded Dr. Earle.
Commenting on the study was ASCO president Bruce E. Johnson, MD, who said, “The use of trastuzumab has been a major advance for women with HER2-positive breast cancer by increasing the cure rate, but no treatment is free of side effects, and heart damage has always been a concern with this treatment. This new trial shows that a shorter length of treatment can benefit patients just as much as a longer treatment, with less risk of cardiac side effects. This is a win-win for patients with breast cancer who are receiving this common treatment.”
This study was funded by the National Institute for Health Research (NIHR), UK.