The PERSEPHONE trial, a £2.6 million study funded by the NIHR with translational research funded by Cancer Research UK, recruited over 4,000 women and compared a six month course of treatment of Herceptin with the current standard of 12 months for women with HER2-positive early-stage breast cancer.
This is the largest trial of its kind examining the impact of shortening the duration of Herceptin treatment. Over the last five years, the NIHR has invested £46.5 million in funding and supporting breast cancer research.
Herceptin, has been a major breakthrough, prolonging and saving the lives of women with breast cancers that carry the HER2 receptor on the surface of their cancer cells. Around 15 out of every 100 women with early breast cancers have HER2 positive disease.
Herceptin is a targeted therapy that works by attaching to the HER2 receptors preventing the cancer cells from growing and dividing. It has rapidly become standard of care and based on clinical research a 12 month treatment course was adopted. However, a further clinical study suggested a shorter duration could be as effective, significantly reducing side effects and cost both to patients and to the NHS.
The trial, led by a team from the University of Cambridge and Warwick Clinical Trials, the University of Warwick, found that 89.4% of patients taking six months treatment were free of disease after four years compared with 89.8% of patients taking treatment for 12 months. These results show that taking Herceptin for six months is as effective as 12 months for many women.
In addition, only 4% of women in the six month arm stopped taking the drug early because of heart problems, compared with 8% in the 12 month arm. Women also received chemotherapy (anthracycline-based, taxane-based or a combination of both) while enrolled in the trial.
Lead study author Professor Helena Earl, Professor of Clinical Cancer Medicine, University of Cambridge and Cancer Research UK Cambridge Centre, said: “The PERSEPHONE trials team, patient advocates who have worked with us on the study and our investigators are very excited by these results. We are confident that this will mark the first steps towards a reduction of Herceptin treatment to six months in many women with HER2-positive breast cancer.
“However, any proposed reduction in effective cancer treatment will always be complex and very challenging, and women currently taking the medication should not change their treatment without seeking advice from their doctor. There is more research to be done to define as precisely as possible the particular patients who could safely reduce their treatment duration. We are poised to do important translational research analysing blood and tissue samples collected within the trial to look for biomarkers to identify subgroups of different risk where shorter/longer durations might be tailored.”
Professor Hywel Williams, Director of the NIHR Health Technology Assessment Programme that funded the PERSEPHONE study said: “This is a hugely important clinical trial that shows that more is not always better. Women will now have the potential to avoid unnecessary side effects of longer treatment without losing any benefit. In turn, this should help save vital funds for the NHS and prompt more studies in other situations where the optimum duration of treatment is not known. It is unlikely that research like this would ever be done by industry, so I am delighted that the NIHR are able to fund valuable research that has a direct impact on patients.”
Professor Charles Swanton, Cancer Research UK’s chief clinician, said: “This is a critically important study that the breast cancer field has been eagerly awaiting. Targeted therapies, while effective, come at a huge health economic cost to the NHS as well as potentially causing side effects such as heart problems. Despite years of research, we haven’t been able to establish the optimal duration of Herceptin treatment, either to delay cancer coming back or to cure patients with early HER2+ breast cancer following surgery.
“The exciting early key findings from this study show that 6 months of Herceptin might be as effective as 12 months, and it may also be safer and with fewer side effects. By analysing tumour and blood samples, the researchers will now try to understand which patients can stop Herceptin at 6 months and which patients need extended therapy.”
Maggie Wilcox, President of Independent Cancer patients Voice (ICPV) who is the patient lead for the PERSEPHONE trial, said: “I am delighted to have been part of this landmark trial which is an important step to reduce the length of treatment whilst not changing effectiveness. Most trials add novel treatments to standard practice whilst this has set out to reduce duration of Herceptin. The collection of the patient reported experiences throughout the trial will greatly inform future practice and benefit patients. ICPV is working with the Persephone team to help disseminate these exciting results’.
The results of the trial, PERSEPHONE, will be presented at the upcoming 2018 ASCO Annual Meeting in Chicago. The full report, which will include analysis to determine the impact of treatment length on quality of life and a detailed cost effectiveness analysis, will publish in the
NIHR journals library
Press release from the NIHR