Friday 12 July 2024
An immunotherapy drug trialled at The Christie NHS Foundation Trust in Manchester which is given before surgery, instead of the standard treatment of surgery and chemotherapy, meant that more than ten times more patients with a certain genetic profile were cancer free after surgery, according to early clinical trial results. This treatment could in the future help between 2,000 and 3,000 bowel cancer patients in the UK every year.
The findings, presented yesterday (2 June 2024) at the American Society of Clinical Oncology (ASCO) Annual Meeting 2024 in Chicago, are interim results from the NEOPRISM-CRC phase II clinical trial to assess whether the immunotherapy drug pembrolizumab can improve outcomes for patients with stage 2 or stage 3 MMR deficient/MSI-High bowel cancer. The trial was a collaboration between UCL (University College London), UCLH, The Christie, St. James’s University Hospital in Leeds, University Hospital Southampton and the University of Glasgow.
In this trial, researchers from UCL recruited 32 patients with stage two or three bowel cancer and a certain genetic profile from five hospitals across the UK. Around 10-15% of patients with stage two or three bowel cancer have the right genetic make-up for this immunotherapy* treatment called pembrolizumab**.
Patients were given nine weeks of pembrolizumab prior to surgery instead of the usual treatment of surgery and chemotherapy, then monitored over time.
Results indicate that over 50% of patients treated with pembrolizumab had no signs of cancer after surgery. This compares to other studies where just 4% of patients treated with pre-operative chemotherapy then surgery had no signs of cancer after surgery.
All of the patients in the trial were still cancer-free many months later. The median cancer-free period was 9.7 months and ranged from 5.3 to 19 months among individual patients.
Over the next few years, the trial will also assess overall survival and relapse rates.
The approach also meant that patients did not require any post-operative chemotherapy, which has side effects and is tough to endure.
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Professor Mark Saunders, consultant clinical oncologist at The Christie said:
“This is a really very exciting new treatment for the 10-15% of patients who have the right genetic make-up. Immunotherapy prior to surgery could well become a game-changer for these patients with this type of cancer. Not only is the outcome better but it saves patients from having more conventional chemotherapy which often has more side-effects.”
“In the future, immunotherapy may well even replace the need for surgery. However, more trials are needed to confirm these promising early results, and The Christie is delighted to collaborate in this way so that we can offer this new form of therapy to our patients as part of the NEOPRISM trial.”
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One of the patients on this trial at The Christie is a woman from Leigh in Greater Manchester, who has proved that age isn’t a barrier when taking part in clinical trials. The 77-year-old is cancer-free thanks to this new immunotherapy treatment.
Eileen Unsworth, who is married to Peter, and has four grown-up children and five grandchildren, initially went to the doctor a year ago with a suspected thyroid problem.
“I take my black Labrador, Annie, on daily walks and started to get breathless, which is unlike me, so went back to my GP. Blood tests showed I had an iron deficiency and was anaemic and further investigations discovered a tumour in my colon and I was diagnosed with stage 3 bowel cancer.” Eileen explained.
In July 2023 Eileen was immediately referred to The Christie where she was told she was suitable to take part in the NEOPRISM clinical trial at the National Institute for Health and Care Research (NIHR) Manchester Clinical Research Facility (CRF) at The Christie which was testing pembrolizumab as a treatment given before surgery for some types of colorectal (bowel) cancer.
“I‘ve never actually felt ill or had any pain. It might seem strange, but I always thought whatever happens I’ll be OK. I never thought I was going to die, and I didn’t even get upset. I told all the children I was going to be OK and not to worry, so nobody did. The only thing we decided to do was cancel our 50th wedding anniversary celebrations last September as I was still having the treatment and wasn’t in the mood.”
Eileen, who had three cycles of pembrolizumab administered via a drip into the arm added:
“The immunotherapy only took 20 minutes, and although I didn’t feel unwell, I always felt so much better after it. It was like a tonic and gave me a boost.”
Eileen was then admitted to The Christie for her planned operation just before Christmas to remove part of the colon and bowel, and she recovered so well she was able to go home on Boxing Day. The immunotherapy was so successful that there was only a microscopic amount of the tumour left at the time of surgery.
“I didn’t mind being in on Christmas day.” She said:
“I got a nice present and a Christmas dinner and my husband visited me with my granddaughter. All the nurses dressed up a bit so there was a lovely atmosphere. I was told that the cancer had responded extremely well to the immunotherapy and that there was no need for chemotherapy. I just go back for scans every few months now.
“I was very surprised when I was offered a trial as I thought people my age weren’t suitable for them, but that’s obviously not the case. The experience has been brilliant, and I’ve not looked back. I feel very lucky. It’s wonderful what they can do now. I’d recommend a clinical trial to anyone. Trust the science.” Eileen added.
Dr Kalena Marti, consultant oncologist at The Christie said:
“In this study we want to understand if giving this immunotherapy drug, pembrolizumab, before surgery improves treatment for bowel cancer for cases where there is a high risk of it returning. We knew the type of bowel cancer Eileen had meant she was likely to respond well to immunotherapy. So instead of going straight in for surgery, we used immunotherapy to shrink her tumour and deal with any other cells to prevent the cancer spreading. We’re really pleased she had such a success outcome before and after surgery and hasn’t suffered any side-effects.”
“Although Eileen was 76 when she was diagnosed, as she was in general good health, her age wasn’t an issue, and we were very happy to recruit her onto the trial. Patients are never too old to take part in research as long as they satisfy the eligibility criteria. Having older people on our trials helps us to better understand how that age group responds to treatment, so they play a vital part in our research.”
Dr Kai-Keen Shiu, Chief Investigator of the trial from UCL Cancer Institute and a Consultant Medical Oncologist at UCLH, said:
“Our results indicate that pembrolizumab is a safe and highly effective treatment to improve outcomes in patients with high-risk bowel cancers, increasing the chances of curing the disease at an early stage. We need to wait to see whether the patients in our trial remain cancer-free over a longer period of time, but initial indications are extremely positive.”
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Bowel cancer is the fourth most common cancer in the UK, with around 42,900 cases a year. Though still predominantly a cancer that affects older people, cases among the under 50s have been increasing in recent decades.
Like many cancers, if bowel cancer is caught early the chances of a positive outcome are high. Nine in ten patients treated for stage one bowel cancer survive for five years or more, but specific sub-types of tumours don’t respond as well to treatment and are more likely to return. Five-year survival falls to 65% in stage three and 10% in stage four bowel cancer.
The phase 2 NEOPRISM commercial clinical trial is still recruiting patients. It is led and sponsored by University College London (UCL) with funding from pharmaceutical company, Merck, Sharp and Dohme and is being conducted by the CRUK and UCL Cancer Trials Centre.
When patients are referred to The Christie to discuss their cancer treatment, details regarding potential clinical trials they may be suitable for will be discussed. Together, the patient and clinical team will decide whether it is appropriate to proceed with a trial or not. More information about taking part in clinical trials can be found here.
*Immunotherapy works by stimulating the body’s own immune system to fight the cancer.
** Pembrolizumab is a type of targeted therapy drug called an immune checkpoint inhibitor (a type of immunotherapy). It works by keeping cancer cells from suppressing the immune system. This allows the immune system to attack and kill the cancer cells. It is currently approved for us in the UK for a wide-range of cancers including breast cancer, melanoma, cervical cancer and some types of lymphomas and carcinomas.