Immunotherapy for bowel cancer could change clinical practice

A large international trial involving UCL and UCLH has found that pembrolizumab, a form of immunotherapy, more than doubled the progression free survival time of patients with a specific subtype of advanced bowel cancer, when compared with chemotherapy. 

Progression free survival is the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse.

The ‘KEYNOTE-177’ Phase III clinical trial, funded by Merck & Co (known as MSD in the UK), recruited 307 patients with metastatic bowel cancer, who had specific DNA mutations known as microsatellite instability high (MSI-H) or mismatch repair deficiency (dMMR). 

These genetic mutations occur when a cell is unable to repair mistakes made during cell division, and when this happens errors in the DNA accumulate and may cause cancer. MSI-H/dMMR can be hereditary (also known as Lynch Syndrome) or sporadic, and affected patients usually have a poor prognosis when the disease has spread to other organs.

As part of an interim analysis, presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, researchers found patients who were treated with pembrolizumab (also known as Keytruda) had progression-free survival of 16.5 months (on average), compared with 8.2 months for those who were treated with chemotherapy +/- bevacizumab or cetuximab antibodies.

In addition, 11% of patients who were treated with pembrolizumab were also found to have a ‘complete response’ where their disease had disappeared from scans. Furthermore in almost half the patients who had pembrolizumab (48.3%), their disease had not progressed after two years versus only a fifth of patients who had had chemotherapy (18.6%), which means the beneficial effects are also durable.

The trial’s UK Chief Investigator, Dr Kai-Keen Shiu, Honorary Associate Professor in Oncology at UCL Cancer Institute and Consultant Medical Oncologist at UCLH, said:  

“This is the first randomised controlled study to show that first-line immunotherapy is significantly better than chemotherapy at shrinking metastatic bowel cancers with these specific DNA mutations, and delaying the time it takes for the cancer to progress.

“Whilst only around five per cent of advanced bowel cancer patients have these genetic mutations, they usually have a worse prognosis, and less response to chemotherapy and other targeted agents.

“The results from this trial really are game-changing and will almost certainly result in a paradigm shift in our current clinical practice.”