Immunotherapy for bowel cancer could change clinical practice

May 29, 2020

A large international trial involving UCL and University College London Hospitals NHS Foundation Trust (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. In a clinical trial, measuring the progression-free survival is one way to see how well a new treatment works.

As part of an interim analysis of clinical trial data, 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.

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."

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 alterations result in cells being unable to repair themselves correctly if damaged, and when this happens, errors in the DNA accumulate which 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.

The randomised controlled trial recruited patients from 23 countries who were put into two equally sized groups. One group (or arm) of patients received pembrolizumab every three weeks for up to 35 cycles of treatment (up to approximately two years), while the other group received standard chemotherapy combinations with cancer targeting drugs bevacizumab or cetuximab (the chemotherapy arm) every two weeks.

Post-treatment resultsUCLH was one of the largest recruiters of patients for the trial with 18 participants from across England and 10 patients received pembrolizumab as first-line treatment.

Dr Shiu added: "The results of the KEYNOTE 177 trial have been keenly awaited by patients, clinicians and scientists alike. It is very encouraging that the side effects of pembrolizumab are significantly less than with chemotherapy, so not only the quantity but also the quality of life of these patients is better on immunotherapy.

"Some of my trial patients had a complete response to this therapy, are very well and have now been in remission for more than three years.

"There is ongoing collaborative research at UCL, UCLH and our research partners to further our understanding of why some patients benefit so much from immunotherapy whilst others do not."

Pembrolizumab is a type of immunotherapy known as a check-point inhibitor and helps make cancer cells more vulnerable to attack by your body's own immune system. It does this by blocking the activity of a molecule called PD-1, thereby allowing T cells (white blood cells that help your body fight disease) attack and kill tumours as they should.

Lead author Professor Thierry André, of the University of Sorbonne, France, said: "Pembrolizumab works in non-randomised studies in this group of patients with advanced disease. This randomised study demonstrates a huge benefit in first line with pembrolizumab and should be the new standard of care."

*These stability figures are accurate. Patients receiving immunotherapy usually either respond well and/or stabilise disease but then their disease does not usually progress or relapse for a long time. Patients on chemotherapy are less likely to have good responses but more disease stabilisation. However, in the majority of all cases, the effect of chemotherapy doesn't last as long unlike the durable benefits of immunotherapy.
-end-


University College London

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.