Immunotherapy significantly increases the number of patients free from bowel cancer

An immunotherapy drug given before surgery instead of chemotherapy meant that significantly more patients with a certain genetic profile were cancer free after surgery, according to clinical trial results presented by researchers at UCL and UCLH.

The findings, presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2024 yesterday, are interim results from the NEOPRISM-CRC phase II clinical trial assessing whether the immunotherapy drug pembrolizumab can improve outcomes for patients with stage 2 or stage 3 MMR deficient/MSI-High bowel cancer.

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.

In this trial, researchers from UCL recruited 32 patients with stage two or three bowel cancer and a certain genetic profile (MMR deficient/MSI-High bowel cancer) from five hospitals across the UK. Around 10-15% of patients with stage two or three bowel cancer have this particular genetic make-up, which represents around 2,000-3,000 cases per year in the UK.

Patients were given nine weeks of pembrolizumab prior to surgery instead of the usual treatment of chemotherapy and surgery, then monitored over time.

Results indicate that 59% of patients had no signs of cancer after treatment with pembrolizumab, with any cancer in the remaining 41% of patients removed during surgery.

All of the patients in the trial were cancer-free after treatment and are 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. When standard care conventional chemotherapy is given to patients with this genetic profile, less than 5% have no signs of cancer after surgery.

The approach also meant patients did not require any post-operative chemotherapy, which has side effects and is tough to endure.

UCLH consultant medical oncologist Dr Kai-Keen Shiu, chief investigator of the trial, 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. NEOPRISM-CRC is a trial that I first thought about in 2019 and am proud of my clinical and research teams at UCLH-UCL, as well as my co-investigators around the country who helped me create and deliver this study within 18 months of opening the trial in 2022. I am most of all thankful to the patients who participated in the trial so far and benefited from this treatment.”

UCLH consultant colorectal surgeon Mr Austin Obichere, who performed surgery at the UCLH trial centre, said: "Surgeons are generally guarded when asked to comment on potential new treatments for bowel cancer. But having seen the astonishing complete disappearance of cancer cells in more than half of trial patients, this new approach holds much promise for the cancer patients it can be offered to.”

And UCLH patient Darren Evans, 47, from Cambridgeshire, said:

“The immune therapy I received before surgery shrunk my tumour from around the size of a golf ball, down to almost nothing. The surgery then removed what was left of the tumour. The therapy did an incredible job at reducing the tumour size, all in around the space of six weeks, with very minimal side effects. I’m really happy I was part of the trial and received the therapy, which I hope will keep the cancer away.”

The research also assessed whether tumour burden could be a useful biomarker to predict individual risk.

The NEOPRISM-CRC trial (NCT05197322) is funded by Merck Sharp and Dohme and is being conducted by the CRUK & UCL Cancer Trials Centre. It is a collaboration between UCL (the study sponsor), UCLH, the Christie NHS Foundation Trust in Manchester, St. James’s University Hospital in Leeds, University Hospital Southampton and the University of Glasgow.

Clinical and research infrastructure and facilities at UCLH and UCL benefit from underlying support from the National Institute for Health and Care Research (NIHR) through the UCLH Biomedical Research Centre (BRC) and Clinical Research Facility (CRF).