ASCO20 Cancer Updates: Immunotherapy Using Pembrolizumab for Colon Cancer Could Revolutionize Clinical Practice

ASCO20 Cancer Updates:  Medical researchers from the University College London (UCL) and University College London Hospitals NHS Foundation Trust (UCLH) in a recent large  international clinical trial have 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.


The term “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.

The interim analysis of clinical trial data, presented at the American Society of Clinical Oncology (ASCO) Annual Meeting indicated that 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.

Furthermore 11% of patients who were treated with pembrolizumab were also found to have a 'complete response' where their disease had disappeared from scans.

Also 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 clinical trial's UK Chief Investigator, Dr Kai-Keen Shiu, Honorary Associate Professor in Oncology at UCL Cancer Institute and Consultant Medical Oncologist at UCLH, told Thailand Medical News,  "This is the first randomized 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. Though 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.”

He further added, "The results from this trial really are game-changing and will almost certainly result in a paradigm shift in our current clinical practice."

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

Typically, 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 extensive randomized controlled trial recruited patients from 23 countries who were p ut 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.

Significant Post-Treatment Findings

-In patients treated with pembrolizumab, progression-free survival was 55.3% at 12 months and 48.3% at 24 months. This compared with 37.3% and 18.6% respectively, for those on chemotherapy.

-It was observed that on an  average patients treated with pembrolizumab had a progression free survival of 16.5 months, compared with 8.2 months of chemotherapy ie an improvement of 8.3 months.

-About 11% of patients receiving pembrolizumab had a complete response (no detectable cancer), compared to 3.9% on chemotherapy.

-Interestingly 32.7% of patients on pembrolizumab had a reduction in tumor size (partial response), compared to 29.2% on chemotherapy.

-Also 30.9% of patients on pembrolizumab had stable disease compared with 42.2% on chemotherapy.

- It was found that response with pembrolizumab was also longer lasting, with 83% of patients having a response longer than 2 years, compared with 35% of patients receiving chemotherapy.

-There were less severe treatment-related adverse events with pembrolizumab, 22%, whereas with chemotherapy this is 66%.

University College London Hospitals NHS Foundation Trust (UCLH) 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.

"The clinical trial findings of the KEYNOTE 177 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," commented Dr Shiu.

The drug 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 tumors as they should.

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

Reference:  Andre T, Shiu K-K, Kim TW, et al: Pembrolizumab vs chemotherapy for microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: The phase 3 KEYNOTE-177 study. ASCO20 Virtual Scientific Program. Abstract LBA4. Presented in premeeting press briefing on May 26, 2020.
 
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