Millions of patients with incurable breast cancer could benefit from Welsh-led research presented today to the world leading cancer research conference in Chicago, ASCO.
The research shows that, by combining investigational therapy with a standard treatment, patients may expect that their cancer will be controlled for twice as long.
Involving 140 patients from 19 hospitals across the UK, the cancer trial called FAKTION is sponsored by Velindre University NHS Trust. It is jointly led by Dr Rob Jones, who co-leads our early phase trials research, and Dr Sacha Howell from the Christie NHS Foundation Trust and University of Manchester.
The 140 patients had all been diagnosed with incurable breast cancer amenable to hormone treatment, known as oestrogen receptor positive cancer.
One of the patients, retired doctor Susan Cunningham from Cardiff was first diagnosed with breast cancer in 2005. She joined the trial in 2017 after she discovered her cancer had spread and was incurable.
“Unfortunately, in my family we have had to break news to my children that a family member has cancer six times. Two grandparents have died of cancer. Another grandparent has had cancer but has fortunately survived. I have had two cancer diagnoses.
“Being on a trial has given me great hope for the future. It’s meant that I have been relatively well for the past two years. Initially I thought I wasn’t going to see my grandchildren but now I have hope that I am going to survive an awful lot longer and see my family grow.”
Dr Rob Jones said, “The incremental benefit from Capivasertib is highly significant and the trial involves patients with a very common form of breast cancer. In the UK for example 55,000 new cases of breast cancer occur each year and about three quarters are oestrogen receptive positive breast cancers. That equates to millions of patients around the world that potentially are going to get benefits from this breakthrough.”
Oestrogen receptive positive breast cancer can be treated by drugs that interfere with the action of oestrogen or the oestrogen receptor. Although these drugs are often effective for a while, the cancer can frequently become resistant and the drugs stop working.
In the trial, researchers investigated whether they could reverse or delay resistance to hormone therapy in post menopausal women whose cancer had spread by adding Capivasertib to existing therapy. Capivasertib is an investigational, targeted therapy which neutralises a cellular protein (called AKT) that has been shown to cause resistance to hormone therapy. Capivasertib was combined with fulvestrant, a hormone therapy which is used to treat secondary breast cancer.
Capivasertib was discovered by AstraZeneca following a collaboration with Astex Therapeutics and its collaboration with the Institute of Cancer Research and Cancer Research Technology Limited.
Angela Casbard, from the Cancer Research UK funded Centre for Trials Research at Cardiff University, said, “In order to look at whether this investigational therapy may be more effective than standard treatment, patients were randomly assigned to receive either Capivasertib in combination with fulvestrant or the standard treatment, fulvestrant, together with a placebo. Neither the treating doctors nor the patients knew who was getting the placebo or Capivasertib. This type of randomised trial is the most effective way of comparing two different treatments.”
Dr Rob Jones said, “The trial was conceived in Wales and it has been wonderful to work with colleagues in the Centre for Trials Research at Cardiff University and to see so many patients treated on the trial here at Velindre Cancer Centre.
“The results are extremely encouraging. We measured success primarily by determining how long the treatment prevented cancer growth, but also whether it resulted in shrinkage of the cancer and how long patients lived for.”
Approximately 70 per cent of patients in the trial had cancer that could be accurately and reliably measured on scans. Careful examination of these scans demonstrated that 41 per cent of patients who received fulvestrant together with Capivasertib experienced a significant shrinkage in their cancer compared to 12 per cent of patients who were allocated to fulvestrant and a placebo.
In addition, patients receiving the Capivasertib had their cancer controlled for an average of 10.3 months whereas for those who got fulvestrant with the placebo it was 4.8 months. The current trial data also suggests that patients treated with the new combination live for an average of six months longer.
Dr Rob Jones said that trials such as FAKTION depend on money gathered through fundraising.
“The NHS often requires additional funding to support research activity like this and obviously Velindre charitable funds is an incredibly important component of that.”
“We are incredibly grateful to all the contributions that enable trials like this to happen. Over the years this has included about a million pounds from Velindre Charitable funds that has supported research staff to deliver all the trials on our Unit"
This research was conducted with support from the investigator-sponsored study collaboration between AstraZeneca and the National Cancer Research Network.
Additional support was provided by the Experimental Cancer Medicine Centre and the National Institute for Health Research (NIHR) Clinical Research Network.
Leaders of the study hope that the research will progress to a phase three trial, where the investigational combination will be tested in a larger number of patients, before any recommendations can be made to take it up as a new standard of treatment on the NHS.