The Christie NHS Foundation Trust in Manchester has piloted a blood test in melanoma, the most serious form of skin cancer, to help determine which treatment to start with, and when to switch.
Preliminary results of the CAcTUS clinical trial, funded by The Christie Charity, show that researchers at the CRUK Cancer Biomarker Centre are able to perform the testing quickly enough to make real-time decisions and that the test is accurate enough to show real-time cancer responses to treatment.
It’s hoped in the future that the blood test, known as a liquid biopsy, will be used regularly to aid doctors in making crucial decisions about when to stop and start different treatments for patients with advanced melanoma.
Professor Paul Lorigan, consultant oncologist at The Christie who is leading on the CAcTUS study said: “We have been using this blood test in real time to identify the best treatment strategy for patients and when to switch to another therapy. The results of the pilot tell us that this could be a huge help in making the right treatment decisions for each individual patient at the right time for them. I hope in the future analysing the tiny pieces of DNA coming from the cancer found in the patient’s blood stream could be commonly used to tell us when a patient is responding to treatment, and when’s the optimum time to change to a new therapy.”
One patient on the trial, José Sotorrio from Chorlton in Manchester, now has no signs of cancer and is looking forward to his milestone 50th birthday in March 2024, thanks to his treatment.
In January 2018, when José was 43, a cancerous mole was removed from his chest and fortunately tests showed it hadn’t spread to any other part of his body. However, exactly three years later, in January 2021, he felt a lump in his armpit which turned out to be a swollen lymph node. When doctors made the devastating discovery that cancer had spread widely, including a 5cm tumour in his right lung, he was diagnosed Stage 4 melanoma.
Because José had detectable tumour DNA (ctDNA)* in his blood, in May 2021 he was told he was eligible for a clinical trial and agreed to take part in research.
The CAcTUS trial involved using 2 different types of treatments in sequence to attack the melanoma in two different ways. One is targeted therapy, which interferes with how cancer cells grow and survive. The other is immunotherapy, which helps the immune system 'see' the melanoma and attack it.
The trial was designed to give targeted therapy to decrease the growth of the cancer until the amount of detectable tumour DNA in the blood dropped by 80%, before any resistance occurred. It was hoped that this would 'prime' the immune system to take notice. Then, by switching to immunotherapy, when the targeted therapy was having optimum effect, the immunotherapy might work better.
José Sotorrio explained: “Growing up in the 70s and 80s, it was normal for me to spend long days on the beach on summer holidays to Spain. People didn’t associate sun exposure with developing skin cancer like they do today. I always hated sunbathing, yet I don't think there are many photos of me as a kid where I don't have a tan.
“Once on the trial, I had a difficult month of high temperatures, vomiting, stopping and restarting treatment due to side-effects, so I wasn't too hopeful that I'd had a consistent enough course of treatment to see results. However, blood tests showed tumour levels in my blood had dropped by over 80% in just 28 days in response to targeted therapy. So doctors decided this was the optimum time to switch from the targeted therapy to immunotherapy.
“Although I was unlucky to get melanoma in the first place, I have to be glad that things have so far worked out for me. It’s possible the specific combination of treatments I had within this clinical trial has saved my life.”
At the end of July 2021, the immune therapy had affected José’s liver function and he had to spend a few days in hospital. Eventually he was able to continue with immunotherapy treatment for two years. His scans showed a complete response to treatment after 12 months and he still has no signs of active cancer.
Dr Rebecca Lee, consultant oncologist and clinician scientist at The Christie who helped develop the trial added: “We’re really pleased José has had a complete response to the treatment. We know that having higher levels of ctDNA in the blood can mean that the cancer is less likely to respond, so potentially reducing the levels with the targeted therapy may have enabled a better response. He now has a very good chance that the melanoma will not come back.
"This trial has shown us that we have a very precise way to monitor cancer activity and can deliver results quick enough to make treatment decisions. Thanks to CAcTUS, we now know we can use this blood test in patients as a tool to guide treatment, which will be important in developing personalised treatment strategies in the future. We have learnt a huge amount and I am extremely proud that the team in Manchester has been able to take our discoveries in the laboratory and begin to test them in the clinic.”
Professor Caroline CBE, Director of the CRUK Cancer Biomarker Centre at The University of Manchester where the test was developed and validated said “we are so delighted that results from the blood testing we performed in our laboratories can be used in real time to advise our clinical colleagues on treatment decisions for patients with melanoma’.
Bristol-Myers Squibb Pharmaceuticals part-funded the study.
This trial is now closed to recruitment. Any patients interested in taking part in clinical trials should discuss this option with their consultant or GP. Not all patients will fit the criteria for a specific trial. While clinical trials can be successful for some patients, outcomes can vary from case to case. You can find more information about taking part in clinical trials in the research section of our website (https://www.christie.nhs.uk/research-and-innovation/studies-and-trials/take-part-in-studies-and-trials).
* Circulating tumour DNA (ctDNA) are small pieces of DNA found in the bloodstream that come from cancerous cells and tumours.