Preoperative immunotherapy prevents more patients from developing colorectal cancer

Press release published on June 3, 2024

An immunotherapy drug being trialed at The Christie NHS Foundation Trust in Manchester was given before surgery instead of chemotherapy, and early clinical trial results showed that many patients with a particular genetic profile were cancer-free after surgery. The treatment could one day help between 2,000 and 3,000 bowel cancer patients in the UK each 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 2 clinical trial, evaluating whether the immunotherapy drug pembrolizumab can improve outcomes for patients with stage 2 or stage 3 MMR-deficient/MSI-high colorectal 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.

For the trial, UCL researchers recruited 32 patients from five hospitals across the UK with stage two or three bowel cancer and a specific genetic profile. Around 10-15% of patients with stage two or three bowel cancer have the right genetic make-up for this immunotherapy* treatment, called pembrolizumab**.

Instead of the usual chemotherapy and surgery, patients were given pembrolizumab for nine weeks before surgery and then observed over time.

According to the results, 59% of patients had no signs of cancer after treatment with pembrolizumab, and the remaining 41% of patients had their cancer removed during surgery.

All patients in the trial were cancer-free after treatment, and still are cancer-free several months later. When patients with this genetic profile are given standard conventional chemotherapy, fewer than 5% have no signs of cancer after surgery.

Over the next few years, the trial will also evaluate overall survival and recurrence rates.

This approach avoids the need for patients to undergo post-operative chemotherapy, which can be fraught with side effects and difficult to tolerate.

Professor Mark Saunders, Consultant Clinical Oncologist at The Christie Hospital, said: “This is truly a very exciting new treatment for the 10-15% of patients who have the right genetic make-up. Immunotherapy before surgery could be a game-changer for patients with this type of cancer. Not only do they have better outcomes, but they would no longer need to undergo traditional chemotherapy, which has many side effects. In future, immunotherapy may even remove the need for surgery. However, more trials are needed to confirm these promising early results. The Christie Hospital is pleased to be working together in this way to bring this new treatment to patients as part of the NEOPRISM trial.”

One of the patients taking part in the trial at The Christie Hospital is a woman from Leigh, Greater Manchester, proving age is no barrier to taking part in a clinical trial: the 77-year-old has beaten cancer thanks to the new immunotherapy.

Eileen Unsworth, who is married to Peter and has four adult children and five grandchildren, first went to see a doctor a year ago for suspected thyroid problems.

“I take my black Labrador, Annie, for walks every day but she started to notice she was breathing unusually shortly afterwards so I went back to my GP. A blood test revealed she was iron deficient and anemic and further tests revealed a tumour in her colon and she was diagnosed with stage three colon cancer,” Eileen explained.

In July 2023, Eileen was quickly referred to The Christie Hospital where she was told she was suitable to take part in the NEOPRISM clinical trial, a trial of the treatment pembrolizumab, administered before surgery for some types of colon cancer.

“I was never actually unwell or in any pain. It may seem strange, but I always felt like whatever happened would be OK. I never thought I was going to die and it didn't faze me. I told all my children not to worry and that I was OK so no one was worried. The only decision we made was to cancel our 50th wedding anniversary celebration last September as I was still undergoing treatment and didn't feel right.”

Eileen, who received three cycles of pembrolizumab via an IV in her arm, added: “The immunotherapy only lasted 20 minutes. I didn't feel sick, but I felt much better after it was over. It gave me energy, like a tonic.”

Eileen was then admitted to Christie Hospital for planned surgery just before Christmas to have part of her colon and intestines removed. She made a good recovery and was able to be discharged on Boxing Day. The immunotherapy was a great success and at the time of surgery only a tiny amount of tumour remained.

“I didn't mind being in hospital on Christmas Day,” she says. “I got lovely presents and Christmas dinner, my husband brought my granddaughter and all the nurses were dressed up a little so it was a lovely atmosphere. I was told that the cancer responded very well to the immunotherapy and that I wouldn't need chemotherapy. I now go back to hospital for scans every few months.”

“I was very surprised when I was offered the clinical trial because I thought it wouldn't be suitable for me at my age, but of course it wasn't. It was a great experience and I don't regret it. I feel very lucky. It's great that clinical trials are available now. I would recommend clinical trials to anyone. Trust the science,” she added.

Dr Karena Martí, consultant oncologist at The Christie Hospital, said: “In this study, we want to see if giving this immunotherapy drug, pembrolizumab, before surgery can have a therapeutic effect in cases of bowel cancer that are at high risk of recurrence. We knew that because of the type of bowel cancer Eileen had, she was likely to respond well to immunotherapy, so rather than going straight for surgery, we used immunotherapy to shrink the tumour and address other cells to stop the cancer spreading. I'm really pleased that she has had such success, both before and after the operation, and has had no side effects.”

“Eileen was 76 years old when she was diagnosed but in general good health, so age was not an issue and we were very happy to have her in the trial. Patients are never too old to take part in a study, provided they meet the eligibility criteria. Including older people in trials gives us a greater understanding of how that age group responds to treatment, so they play an important role in our research.”

Dr Kai Kean Xu, lead investigator of the trial at the Institute of Cancer Research, University of London and consultant medical oncologist at University Hospital London, said: “Our findings show that pembrolizumab is a safe and highly effective treatment that improves outcomes for patients with high-risk colorectal cancer and increases the chances of curing the disease early. We do not yet know whether patients in our trial will remain cancer-free for the long term, but the early signs are very encouraging.”

Bowel cancer is the fourth most common cancer in the UK, with around 42,900 cases per year. Although bowel cancer remains predominantly a cancer that affects older people, there has been an increase in cases in people under 50 over recent decades.

Like many cancers, colon cancer has a good chance of a positive outcome if it is detected early. Nine out of 10 patients treated for stage 1 colon cancer survive at least five years, but certain subtypes of tumors respond less well to treatment and are more likely to recur. The five-year survival rate drops to 65% for stage 3 colon cancer and 10% for stage 4 colon cancer.

NEOPRISM's Phase 2 commercial clinical trial is still recruiting patients. The trial is led and sponsored by University College London (UCL) and conducted by CRUK and the UCL Cancer Trials Centre, with funding from pharmaceutical companies Merck, Sharp and Dome.

When a patient is referred to The Christie to discuss cancer treatment, we will discuss details of any clinical trials the patient may be able to participate in. Together, the patient and the clinical team will decide whether it is appropriate to proceed with the trial. For more information about participating in a clinical trial, Participate in research and trials.

*Immunotherapy works by stimulating the body's own immune system to fight cancer.

** Pembrolizumab is a type of targeted therapy called an immune checkpoint inhibitor (a type of immunotherapy). It works by stopping cancer cells from suppressing the immune system. This allows the immune system to attack and kill the cancer cells. It is currently approved in the UK to treat a wide range of cancers, including breast cancer, melanoma, cervical cancer and some types of lymphoma and cancer.