• Vall d’Hebron has taken part in a clinical trial that could change clinical practice in patients with this subtype of advanced metastatic colorectal cancer
  • It is the first time a treatment using only the anti-PD1 antibody pembrolizumab and not including chemotherapy has proved effective as a first-line treatment in patients with colorectal cancer with microsatellite instability
  • Pembrolizumab shows a more favorable tolerance profile than standard treatments

Barcelona, May 31, 2020.– Immunotherapy without chemotherapy could be the way forward for treating some types of colorectal cancer after it has proved for the first time to be more effective than the standard treatment. Pembrolizumab, an anti-PD-1 antibody, has shown positive results in the KEYNOTE-177 study, which assessed its effectiveness and safety compared with standard chemotherapy treatment in metastatic colorectal cancer patients with microsatellite instability. The results of the study, in which the Vall d’Hebron Institute of Oncology (VHIO) – part of the Vall d’Hebron Campus – played an outstanding role could lead to a change of paradigm in the treatment of these patients. The study is so important that it will be the subject of a plenary session at the American Society of Clinical Oncology (ASCO), which is being held virtually this year.

Dr. Elena Élez, a medical oncologist at the Vall d’Hebron University Hospital and a researcher in the Gastrointestinal and Endocrine Tumors Group at the VHIO, took part in the work. “The importance of this study lies in the fact that it is the first time an immunotherapy drug administered alone – in other words without added chemotherapy – demonstrates superiority to standard of care in the first-line treatment for metastatic colorectal cancer”, said Dr. Élez.

Patients with poor prognosis
Microsatellite instability is a change that occurs in the DNA of certain cells in which the number of microsatellite repeats – short, repeated DNA sequences – is different from the number of repetitions in the DNA when it was inherited. The cause of this instability can be a defect in the capacity to repair errors occurring when the DNA is copied in the cell. “About 15% of colorectal tumors have this molecular alteration. When the disease is metastatic – in other words, when it has spread – this percentage is lower but it can also mean a worse prognosis,” said Dr. Élez.

As a result of this microsatellite instability the level of mutations is high, giving rise to what are known as hypermutated tumors. This means the proteins generated from the mutations behave as neoepitopes – regions of antigens generated by modification of the original antigen which can be recognized by the immune system. “This is why these tumors respond very well to immunotherapy. We had already found that pembrolizumab alone already had positive results in patients with metastatic colorectal cancer with microsatellite instability refractory to other treatments. Now we can see that, as a first-line treatment, it can also be a very effective alternative with an excellent tolerance profile,” added Dr. Élez.

More effective in all areas
The study, which included a total of 307 patients with advanced metastatic colorectal cancer with microsatellite instability, compared the effectiveness of pembrolizumab as a monotherapy and first-line treatment with the standard treatment: combined chemotherapy and immunotherapy.

The first finding was a clearly significant improvement in progression-free survival time. With the standard treatment this was 8.2 months but, in the study using pembrolizumab alone, the figure was 16.5 months – more than double the time. “We have also seen a better confirmed response rate, rising from 33% in the standard treatment to 43% with pembrolizumab. The right tolerance profile is also an added value in this treatment strategy,” said Dr. Élez.

In addition, only 22% of the patients who received pembrolizumab treatment showed any kind of adverse side effects. This rose to 66% of the patients following the standard treatment including chemotherapy. “For all these reasons, we believe we are looking at a change of paradigm in the treatment of advanced colorectal cancer. Once again, it has been shown that knowledge of the molecular biology of these tumors plays a fundamental role in developing new treatment strategies, achieving not only a clear improvement in survival but also improving the toxicity profile and reducing the side effects suffered by our patients,” concluded Dr. Élez.