A new study co-led by the University of Warwick Clinical Trials Unit has shown that shortening the duration of a therapy for breast cancer patients does not increase the risk of their cancer returning.
The majority of clinical trials in cancer assess either new treatments or additional treatments to the current standard of care. However equally important questions for patients and healthcare teams concern reduction in the length of treatments and attendant toxicities and whether this can be achieved without any worsening of outcomes. Clinical trial results published in the Lancet today (6 June) show that women treated with 6 months of Herceptin for HER2 positive early breast cancer did as well in terms of their risk of breast cancer returning as those getting the currently conventional 12 months treatment. Six months also significantly reduced treatment related side effects, including heart problems.
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 with HER2-positive early-stage breast cancer. It compared a six month course of Herceptin with the current standard of twelve months to see whether the shorter treatment was similar to or no worse than the longer treatment. This is the largest trial of its kind examining the impact of shortening the duration of Herceptin
The trial, led by a team from the University of Cambridge and the Clinical Trials Unit at the University of Warwick, involved 4088 women and is larger than any previous study in this field. It found that 89.4% of patients taking six months treatment were free of breast cancer after four years compared with 89.8% of patients taking treatment for twelve months. These results show that women who took Herceptin for six months fared no worse than patients who had standard 12 months treatment in terms of breast cancer returning. In addition, only 3% of women in the six month arm had to stop taking the drug because of heart problems compared with 8% in the 12 month arm. This trial mapped onto standard practice in the NHS where both chemotherapy and Herceptin are given before or after surgery.
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. Based on clinical trials a twelve month treatment course was adopted as standard with a requirement for 18 three-weekly injections. However, a further clinical study, the FinHer trial hinted that a shorter duration might be as effective, significantly reducing side effects and cost both to patients and to healthcare systems. The NIHR therefore funded this study to compare the standard 12 months of therapy with a shorter 6 month course.
Professor Janet Dunn who led the trial at Warwick Clinical Trials Unit said: “The NIHR is a great funder for these types of trials as they ultimately refine treatment for patients with the maximum patient benefit ensured. Data collected on the patient reported experiences confirm the tough time patients have going through treatment and the impact any treatment has on their longer term quality of life.”
Lead study author Professor Helena Earl, Professor of Clinical Cancer Medicine, University of Cambridge and Cancer Research UK Cambridge Centre said “We would like to thank the 4088 patients who took part in our study and the tireless efforts and dedication of the trial teams at both Warwick and Cambridge. The trial would not have been possible without support from the NHS Clinical Research Network for the 152 teams at centres throughout the UK who recruited patients. In addition, the PERSEPHONE trials team has benefited enormously from an invaluable partnership with patient advocates throughout the study.
“The trial included patients who were receiving or going to receive Herceptin as standard in the NHS for HER2 positive breast cancer. The result indicates there are a large number of patients where a reduced Herceptin treatment duration of six months provides a similar benefit to 12 months without the risk of additional side effects. This data can now be added to all existing data on adjuvant Herceptin to be scrutinized by the wider breast cancer community for consideration of changes to practice. The study does however also suggest that there may be groups where the longer duration is needed to achieve maximum benefit. Women currently taking the medication should not change their treatment without seeking advice from their doctor. There is research to be done to define more precisely women who can 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 where shorter or longer durations might be tailored.”
The trial has also collected qualitative research data on patient reported experiences on Herceptin. Common side effects reported in up to a third of women are aches/pains and fatigue with significant effects on daily functioning and quality of life. Cost savings for 6 months Herceptin compared with 12 months were presented at the ESMO conference in October 2018, and have been estimated at £9,699 per patient. Detailed cost effectiveness analysis including a life-time model, subgroup analyses and a societal cost analysis are underway. Given that HER2+ breast cancer represents a significant global burden of the disease, 6 months adjuvant treatment would translate into potential global savings of hundreds of millions of dollars annually. Worldwide this will have huge impact in middle and low income countries since it will facilitate Herceptin treatment (a World Health Organisation designated essential medicine) for many more women with HER2 positive early breast cancer.
Professor Charles Swanton, Cancer Research UK’s chief clinician, said: “Cancer Research UK’s work paved the way for the development of Herceptin, which has saved the lives of many thousands of women with breast cancer. But 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 positive breast cancer following surgery.
“These eagerly anticipated results give the breast cancer research community an opportunity to reassess how long to give this targeted therapy to patients to see them living longer and with a better quality of life.
“The important next steps are to work out which patients can stop Herceptin at 6 months and which 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, published in the Lancet today were presented at the June, 2018 ASCO Annual Meeting in Chicago, The full report, which will include analysis to determine the impact of treatment length on quality of life with patient reported experiences and a detailed cost effectiveness analysis, will be published in the NIHR journals library. Visit the project page for more information.
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For more information about the PERSEPHONE trial, please visit:
Cancer Research UK figures: Around 55,200 people are diagnosed with breast cancer in the UK each year, based on the annual average number of new cases of breast cancer (ICD10 C50) diagnosed between 2014-2016 in the United Kingdom.
About 15 out of every 100 women (around 15%) with early breast cancer have HER2 positive cancer. http://www.cancerresearchuk.org/about-cancer/breast-cancer/getting-diagnosed/tests-diagnose/hormone-receptor-testing-breast-cancer
Notes to Editors:
About Warwick Clinical Trials Unit
- Warwick Clinical Trials Unit (WCTU) is an academic unit based in the Medical School in the University of Warwick. It runs clinical trials in academic partnership with clinicians throughout the UK. It has full UKCRC registration and is one of the NCRI group of CTUs with excellence in conducting cancer clinical trials. For further information please visit: https://warwick.ac.uk/fac/sci/med/research/ctu/.=
About the NIHR
The National Institute for Health Research (NIHR) is the nation's largest funder of health and care research. The NIHR:
· Funds, supports and delivers high quality research that benefits the NHS, public health and social care
· Engages and involves patients, carers and the public in order to improve the reach, quality and impact of research
· Attracts, trains and supports the best researchers to tackle the complex health and care challenges of the future
· Invests in world-class infrastructure and a skilled delivery workforce to translate discoveries into improved treatments and services
· Partners with other public funders, charities and industry to maximise the value of research to patients and the economy
The NIHR was established in 2006 to improve the health and wealth of the nation through research, and is funded by the Department of Health and Social Care. In addition to its national role, the NIHR commissions applied health research to benefit the poorest people in low- and middle-income countries, using Official Development Assistance funding.
This work uses data provided by patients and collected by the NHS as part of their care and support and would not have been possible without access to this data. The NIHR recognises and values the role of patient data, securely accessed and stored, both in underpinning and leading to improvements in research and care. www.nihr.ac.uk/patientdata
- Independent cancer patients’ voice (ICPV) is a registered charity (no.1138456) who work in partnership with researchers. Clinical research is improved by patients being partners with clinicians and healthcare professionals rather than passive recipients of healthcare.
- Please see http://www.independentcancerpatientsvoice.org.uk/ for further information.
About Cancer Research UK
- Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research.
- Cancer Research UK’s pioneering work into the prevention, diagnosis and treatment of cancer has helped save millions of lives.
- Cancer Research UK receives no funding from the UK government for its life-saving research. Every step it makes towards beating cancer relies on vital donations from the public.
- Cancer Research UK has been at the heart of the progress that has already seen survival in the UK double in the last 40 years.
- Today, 2 in 4 people survive their cancer for at least 10 years. Cancer Research UK’s ambition is to accelerate progress so that by 2034, 3 in 4 people will survive their cancer for at least 10 years.
- Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses.
- Together with its partners and supporters, Cancer Research UK's vision is to bring forward the day when all cancers are cured.
About the Cancer Research UK Cambridge Centre
- We’re one of two Cancer Research UK Major Centres, based in Europe’s largest Biomedical Campus, and supporting a network of 11 Centres across the UK.
- Our Centre unites more than 600 laboratory researchers and healthcare professionals working across the University of Cambridge and allied Institutions, and Cambridge University Hospitals and Royal Papworth Hospital NHS Foundation Trusts.
- Members populate 12 Programmes – the engines of our research – with a particular focus on early detection, personalised and integrated cancer medicine, and cancers of unmet need (brain, lung, oesophageal, pancreatic).
- Each programme facilitates intra- and inter-programmatic research to drive the translation of the latest innovations in cancer science scientific discoveries into clinical applications to improve patient care.
- Our overarching strategy is to develop a proactive approach to cancer that diagnoses the disease as soon as possible and treats each patient precisely.
- To support our strategy, we are building the first National Institute for the Early Detection of Cancer and an Institute for Integrated Cancer Medicine. These are pioneering new approaches to cancer treatment to diagnose and treat cancer patients more quickly and more accurately.
- The Centre is the host of a new Cancer Research UK Children’s Brain Tumour Centre of Excellence.
- Centre members are leading two Cancer Research UK Grand Challenge Projects.
- In recognition of our global reputation as a leading cancer research centre are:
- A founding member of Cancer Core Europe.
- A Comprehensive Cancer Centre designated by the Organisation of European Cancer Institutes (2013).
- A Comprehensive Cancer Center of Excellence designated by the European Academy of Cancer Sciences (2017), one of two just Centres in Europe to receive this award.
About Cambridge University Hospitals
- Cambridge University Hospitals (CUH) is one of the largest and best known hospitals in the country, delivering high-quality patient care through Addenbrooke’s and the Rosie Hospitals. CUH is a leading national centre for specialist treatment for rare or complex conditions and a university teaching hospital with a worldwide reputation.
- CUH is a key partner in Cambridge University Health Partners (CUHP), one of only six academic health science centres in the UK, and is at the heart of the development of the Cambridge Biomedical Campus (CBC), which brings together on one site world-class biomedical research, patient care and education. As part of the Campus development, Papworth Hospital is creating a bespoke, purpose-built hospital, and AstraZeneca is building a new global R&D centre and corporate headquarters. The Campus is one of the government’s National Institute for Health Research (NIHR) comprehensive biomedical research centres.
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